DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION
 

Advisory Committee on

Immunization Practices (ACIP) 

Summary Report

October 19-20, 2016
 

Atlanta, Georgia
 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Table of Contents Page 

Agenda 5-6 

Acronyms 7-10 

Wednesday: October 19, 2016 

Welcome and Introductions 11-14 

Hepatitis Vaccine 

 Introduction 

 Updated Hepatitis B Vaccine Recommendations 

 VFC Resolution 

15-31 

Pertussis Vaccines 

 Introduction 

 Guidance on Timing of Tdap Administration During Pregnancy 

 Public Comments 

 Updated ACIP Statement for Pertussis, Tetanus, and Diphtheria Vaccines 

31-46 

Human Papillomavirus (HPV) Vaccines 

 Introduction 

 Review of Evidence for 2-Dose Vaccine Schedule 

 Proposed Recommendations for 2-Dose HPV Vaccination 

 Public Comment 

 Recommendation Vote 

 VFC Resolution 

46-64 

Meningococcal Vaccines 

 Introduction 

 Impact of MenB-FHbp (TRUMENBA®) on Meningococcal Carriage 

 Immunogenicity Studies of Two MenB Vaccines in Adults 

 MenB-FHbp Update 

 Consideration for us of 2- and 3-Dose Schedules of MenB-FHbp 

 Public Comment 

 Recommendation Vote 

 VFC Resolution 

64-89 

Herpes Zoster Vaccines 

 Introduction 

 Herpes Zoster Background 

 Herpes Zoster Vaccine Update : Herpes Zoster Subunit (HZ/su) Vaccine 

90-101 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Yellow Fever Vaccine 

 Update on Vaccine Supply 101-105 

Public Comment 105-106 

Thursday: October 20, 2016 

Zika Virus Update 107-111 

Agency Updates 

 Centers for Disease Control and Prevention (CDC) 

 Center for Medicare and Medicaid Services (CMS) 

 Department of Defense (DoD) 

 Department of Veteran’s Affairs (DVA) 

 Food and Drug Administration (FDA) 

 Heath Resources and Services Administration (HRSA) 

 Indian Health Services (I HS) 

 National Institutes of Health (NIH) 

 National Vaccine Advisory Committee (NVAC) 

 National Vaccine Program Office (NVPO) 

111-117 

Child / Adolescent Immunization Schedule 

 Introduction 

 Child / Adolescent Immunization Schedule 

117-122 

Adult Immunization Schedule 

 Introduction 

 Adult Immunization Schedule 

123-135 

Pneumococcal Vaccine 

 Introduction 

 Direct and Indirect Impact of PCV13 Use on Invasive Disease Among Adults and Children in 

the US 

 Changes in Invasive Disease Burden Among Adults With and Without Indications for PCV13 

Use 

 Outline of Research Agenda to Inform Potential Policy Change in 2018 or PCV13 Use 

Among Adults 

136-154 

Influenza 

 Introduction 

 Epidemiology / Surveillance Update 

 AFLURIA® Quadrivalent Influenza Vaccine 

154-160 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Respiratory Syncytial Virus (RSV) Vaccine 

 Introduction 

 Burden of Disease in Older Adults 

 Update on Novavax RSV Vaccine Development Programs 

160-174 

Evidence-Based Recommendations 174-176 

Vaccine Supply 177 

Public Comment 177 

Certification 178 

Membership Roster 179-187 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Acronyms 

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics 

AASLD American Association for the Study of Liver Diseases 

ABCs Active Bacterial Core surveillance 

ACIP Advisory Committee on Immunization Practices 

ACNM American College of Nurse Midwives 

ACOG American Congress of Obstetricians and Gynecologists 

ACP American College of Physicians 

AE Adverse Events 

aHCST Autologous Hematopoietic Stem Cell Transplant 

AIM Association of Immunization Managers 

ALT Alanine Aminotransferase 

ASPR Assistant Secretary for Preparedness and Response 

BARDA Biomedical Advanced Research and Development Authority 

BV Baculovirus 

BBB Blood-Brain Barrier 

BIO Biotechnology Innovation Organization 

BLA Biologics License Application 

CAP Community-Acquired Pneumonia 

CAPiTA Community-Acquired Pneumonia Immunization Trial in Adults 

CBER Center for Biologics Evaluation and Research 

CCA Chimpanzee Coryza Agent 

CDC Centers for Disease Control and Prevention 

C-Section Cesarean Section 

CHeRP Center for Healthcare Research in Pediatrics 

CI Confidence Interval 

CICP Countermeasures Injury Compensation Program 

CISA Project Clinical Immunization Safety Assessment Project 

CKD Chronic Kidney Disease 

CLD Chronic Liver Disease 

cLIA Competitive Luminex Immunoassay 

CMS Center for Medicare and Medicaid 

COI Conflict of Interest 

COID Committee on Infectious Disease, AAP 

CONUS Continental United States 

COPD Chronic Obstructive Pulmonary Disease 

DFO Designated Federal Official 

DGSOM David Geffen School of Medicine 

DIR Division of Intramural Research 

DLA Defense Logistics Agency 

DMID Division of Microbiology and Infectious Diseases 

DNA Deoxyribonucleic Acid 

DoD Department of Defense 

DRC Democratic Republic of the Congo 

DSMB Data Safety Monitoring Board 

DTaP Diphtheria and Tetanus Toxoid and Pertussis 

DVA Department of Veterans Affairs 

ED Emergency Department 

EHDB Enteric and Hepatic Diseases Branch 

eHMP Enterprise Health Management Platform 

EHR Electronic Health Record 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

EIA Enzyme Immunoassay 

EMR Electronic Medical Record 

EPS Enhanced Pertussis Surveillance 

EtD Evidence to Decision 

EtR Evidence to Recommendation 

FDA Food and Drug Administration 

FHA Filamentous Hemagglutinin 

Fiocruz Fundacao Oswaldo Cruz-Fiocruz 

FIM Fimbria 

GBS Guillain-Barré Syndrome 

GI Gastrointestinal 

GID Global Immunization Division 

GMC Geometric Mean Concentrations 

GMT Geometric Mean Titers 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

GSK GlaxoSmithKline 

HBeAg Hepatitis B e Surface Antigen 

HBsAg Hepatitis B Surface Antigen 

HBV Hepatitis B Vaccine 

HCP Healthcare Personnel 

HCV Hepatitis C Virus 

HepB Hepatitis B 

HepB-BD HepB Birth Dose 

HZ Herpes Zoster 

HZ/su HZ Subunit Vaccine 

HHS (Department of) Health and Human Services 

HI Hemagglutination Inhibition 

Hib Haemophilus Influenzae Type B 

HIV Human Immunodeficiency Virus 

HMO Health Maintenance Organization 

hMPV Human Metapneumovirus 

HPV Human Papillomavirus 

HRSA Health Resources and Services Administration 

hSBA Human Complement Serum Bactericidal Antibody 

ICD International Classification of Diseases 

ICG International Coordinating Group 

ICU Intensive Care Unit 

IDSA Infectious Disease Society of America 

IgG Immunoglobulin G 

IHR International Health Regulations 

IHS Indian Health Service 

IIV Inactivated Influenza Vaccine 

ILI Influenza-Like Illness 

IMS Insurance Management Services 

IND Investigational New Drug 

IPD Invasive Pneumococcal Disease 

ISO Immunization Safety Office 

JE Japanese Encephalitis 

LAIV Live Attenuated Influenza Vaccine 

LRTI Lower Respiratory Tract Illness 

MenACWY Quadrivalent Meningococcal Conjugate Vaccine 

MenB Serogroup B Meningococcal Disease 

MI Myocardial Infarction 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

MIWG Maternal Immunization Working Group 

MMWR Morbidity and Mortality Weekly Report 

MoH Ministry of Health 

MSM Men Who Have Sex With Men 

msLRTD Moderate to Severe Lower Respiratory Tract Disease 

mTVC Modified Total Vaccinated Cohort 

NACCHO National Association of County and City Health Officials 

NAIIS National Adult and Influenza Immunization Summit 

NAM National Academy of Medicine 

NCEZID National Center for Emerging and Zoonotic Infectious Diseases 

NCHHSTP National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

NCHS National Center of Health Statistics 

NCIRD National Center for Immunization and Respiratory Diseases 

NCQA National Committee for Quality Assurance 

NEJM New England Journal of Medicine 

NFID National Foundation for Infectious Diseases 

NHANES National Health and Nutrition Examination Survey 

NHIS National Health Interview Survey 

NIAID National Institute of Allergy and Infectious Diseases 

NIC National Immunization Conference 

NICHD National Institute of Child Health and Human Development 

NIH National Institutes of Health 

NIMH National Institute of Mental Health 

NNDSS National Notifiable Diseases Surveillance System 

NVAC National Vaccine Advisory Committee 

NVP National Vaccine Plan 

NVPO National Vaccine Program Office 

OMB Office of Management and Budget 

PAHO Pan American Health Organization 

PCA Palivizumab-Competing Antibodies 

PCR Polymerase Chain Reaction 

PCV13 Pneumococcal Conjugate Vaccine 

PEP Post-Exposure Prophylaxis 

PhRMA Pharmaceutical Research and Manufacturers of America 

PHR Public Health Reports 

pIMDs Potential Immune Mediated Diseases 

PPSV23 Pneumococcal Polysaccharide Vaccine 23 

PPB Prime-Prime-Boost 

PRN Pertactin 

PT Pertussis Toxin 

QALYs Quality Adjusted Life Years 

QIV Quadrivalent Influenza Vaccine 

qPCR Real-Time Polymerase Chain Reaction 

RCT Randomized Controlled Trial 

RIV Recombinant Influenza Vaccine 

RNA Ribonucleic Acid 

RSV Respiratory Syncytial Virus 

RSV-ARD RSV-Acute Respiratory Disease 

RT-PCR Reverse Transcriptase Polymerase Chain Reaction 

SAEs Serious Adverse Events 

SAGE Strategic Advisory Group of Experts on Immunization 

sBLA Supplemental Biologics License Application 

SCR Seroconversion Rate 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

SES Socioeconomic Status 

SGA Small for Gestational Age 

SME Subject Matter Experts 

Sf9 Spodoptera frugiperda Cell Line 

SSUAD Serotype-Specific Urine Antigen Detection 

Tdap Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis 

TIV Trivalent Influenza Vaccine 

TVC Total Vaccinated Cohort 

UAT Urine Antigen Test 

UCLA University of California at Los Angeles 

UCSF University of California, San Francisco 

UK United Kingdom 

UN United Nations 

US United States 

VAERS Vaccine Adverse Event Reporting System 

VE Vaccine Efficacy 

VFC Vaccines for Children 

VICP Vaccine Injury Compensation Program 

VistA Veterans Information Systems and Technology Architecture 

VLP Virus-Like Particle 

VSD Vaccine Safety Datalink 

VSV Vesicular Stomatitis Virus 

VZV Varicella Zoster Virus 

WG Work Group 

WGS Whole Genome Sequencing 

WHO World Health Organization 

WNV West Nile Virus 

WRAIR Walter Reed Army Institute of Research 

YF Yellow Fever 

ZIP Zika in Infants and Pregnancy Study 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Call To Order, Welcome, Overview / Announcements, & Introductions 

Call To Order / Welcome 

Nancy Bennett, MD, MS 

ACIP Chair 

Dr. Bennett called the October 2016 Advisory Committee on Immunization Practices (ACIP) 

meeting to order and welcomed those present. 

Overview / Announcements 

Amanda Cohn, MD 

Executive Secretary, ACIP / CDC 

Dr. Cohn welcomed everyone to the October 2016 ACIP meeting. She indicated that the 

proceedings of this meeting would be accessible to people not in attendance via the World Wide 

Web, and welcomed those who could not attend the meeting in person. She then recognized 

several others in the room who were to be present throughout the duration of the meeting to 

assist with various meeting functions: Ms. Natalie Greene and Dr. Jean Clare Smith. She 

noted that handouts of the presentations were distributed to the ACIP members and were made 

available for others on the tables outside of the auditorium. Slides presented during this 

meeting will be posted on the ACIP website approximately two weeks after the meeting 

concludes after being made visually accessible to all viewers, including the visually disabled. 

The live webcast will be posted within four weeks following the meeting, and the meeting 

minutes will be available on the website within approximately 90 days following this meeting. 

Members of the media interested in conducting interviews with ACIP members were instructed 

to contact Ian Branam, located at the press table, for assistance in arranging interviews. 

The next ACIP meeting will be convened at the Centers for Disease Control and Prevention 

(CDC) on Wednesday and Thursday, February 22-23, 2017. Registration for all meeting 

attendees is required. The registration deadline for Non-US citizens is February 1, 2017 and for 

US citizens registration closes February 13, 2017. Registration is not required for webcast 

viewing. As a reminder for non-United States (US) citizens attending ACIP meetings, 

completion of several forms is required for each meeting at the time of registration. It is 

important that these forms are submitted within the required time frame. Stephanie Thomas, 

the ACIP Committee Management Specialist, will be able to help with any questions about the 

process. 

Dr. Cohn introduced and welcomed Dr. Allen Craig who recently joined the National Center for 

Immunization and Respiratory Diseases (NCIRD) as the Deputy Director. Dr. Craig was most 

recently part of CDC’s Global Immunization Division (GID) where he served as the Africa Team 

Lead in the Polio Eradication Branch since 2013. After completing his medical residency, Dr. 

Craig joined the Indian Health Service where he served as the Acting Chief Medical Officer from 

1993 to 1995. In 1995, he joined the Tennessee Department of Health and later became a 

State Epidemiologist before returning to CDC in 2007. He was an ACIP member for a short 

duration of time before he joined CDC. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Dr. Cohn introduced the following guests attending this ACIP meeting: 

 Dr. Lu Ming, EPI Division Director, Ministry of Health (MoH) 

 Dr. Feng Zijian, Deputy Director of China CDC 

 Dr. Wang Huaqing, National Immunization Program Director, China CDC 

 Dr. An Zhijie, Vaccine Evaluation Division Director, China CDC 

 Dr. Xu Keming, External Affairs and Communication Division Director, Ministry of Health 

 Dr. Xia Wei, National Professional Officer, World Health Organization (WHO) China Office 

 Dr. Su Qiru, Epidemiologist, China CDC 

 Dr. Lance Rodewald, CDC Medical Officer on Secondment to WHO China 

Dr. Cohn reported the following Ex Officio and Liaison Representative substitutions during this 

meeting: 

Ex Officio Members 

 Ms. Kathleen Pittman is representing the US Department of Veterans Affairs (DVA) 

 Dr. Gus Birkhead is representing the National Vaccine Program Office (NVPO) 

Liaison Representatives 

 Dr. Corey Robertson is representing Pharmaceutical Research and Manufacturers of 

America (PhRMA) 

 Dr. Bonnie Maldonado is representing the Committee on Infectious Diseases (COID) of the 

American Academy of Pediatrics (AAP) 

 Dr. Greg Frank is representing Biotechnology Innovation Organization (BIO) 

 Dr. Susan Lett is representing the Association of Immunization Managers (AIM) 

Regarding public comments, Dr. Cohn indicated that topics presented during ACIP meetings 

include open discussion with time reserved for public comment. She explained that time for 

public comment pertaining to topics on the agenda was scheduled following the end of the day’s 

sessions, and that time for public comments also would be provided prior to each vote by ACIP 

to enable these comments to be considered before a vote. Registration for public comments is 

solicited in advance of meetings. People who planned to make public comments were 

instructed to visit the registration table at the rear of the auditorium where Ms. Natalie Greene 

would record their name and provide information on the process. People making public 

comments were instructed to provide 3 pieces of information: name, organization if applicable, 

and any conflicts of interest (COI). Registration for public comment also was solicited in 

advance of this meeting through the Federal Register. Given time constraints, each comment 

was limited to 3 minutes. Participants unable to present comments during this meeting were 

invited to submit their comments in writing for inclusion in the meeting minutes. 

Recommendations and immunization schedules can be downloaded from the ACIP website. 

ACIP has a policy that every three to five years each recommendation is reviewed, and then 

renewed, revised, or retired. During every meeting, an update is provided on the status of ACIP 

recommendations. There was one ACIP publication since the June 2016 meeting, which is 

reflected in the following table: 

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 www.cdc.gov/vaccines/acip/index.html 

Introduction of New Members / Roll Call 

 

Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Applications for ACIP membership are due no later than August 2, 2017 for the 4-year term 

beginning July 1, 2018. Detailed instructions for submission of names of potential candidates to 

serve as ACIP members may be found on the ACIP web site: 

E-mail: acip@cdc.gov Web homepage:

Nominations: www.cdc.gov/vaccines/acip/committee/req-nominate.html 

A current CV, at least one recommendation letter from a non-federal government employee, and 

complete contact information are required. These may be submitted as e-mail attachments to

Dr. Jean Clare Smith at jsmith2@cdc.gov 

To summarize COI provisions applicable to the ACIP, as noted in the ACIP Policies and

Procedures manual, members of the ACIP agree to forgo participation in certain activities

related to vaccines during their tenure on the committee. For certain other interests that 

potentially enhance a member’s expertise while serving on the committee, CDC has issued 

limited COI waivers. Members who conduct vaccine clinical trials or serve on data safety

monitoring boards (DSMBs) may present to the committee on matters related to those vaccines, 

but these members are prohibited from participating in committee votes on issues related to 

those vaccines. Regarding other vaccines of the concerned company, a member may

participate in discussions, with the proviso that he/she abstains on all votes related to the

vaccines of that company. It is important to note that at the beginning of each meeting, ACIP 

members state any COIs. 

Nancy Bennett, MD, MS

ACIP Chair 

Dr. Bennett introduced the following new ACIP members, who will serve a 4-year term from July 

2016 through June 2020: 

 Robert Atmar, MD is Board Certified in Internal Medicine and Infectious Diseases, has

served joint appointments since 2006 as Professor of Medicine and Professor of Molecular

Virology and Microbiology at the Baylor College of Medicine. He has served since 2007 as

Chief of the Infectious Diseases Service at Ben Taub General Hospital. In addition to his

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Advisory Committee on Immunization Practices (ACIP) 	 Summary Report October 19-20, 2016 

strong record of basic and clinical research, Dr. Atmar has contributed generously to the 

administrative, clinical, and educational missions of the college. 

 Paul Hunter, MD is Board Certified in Family Medicine. He has served since 2009 as 

Associate Medical Director of the City of Milwaukee Health Department in Milwaukee, 

Wisconsin, Wisconsin’s largest and most ethnically diverse city, with public health problems 

related to disparities within the city’s population. He also is Associate Professor in the 

Department of Family Medicine and Community Health, School of Medicine and Public 

Health, at the University of Wisconsin Madison. Dr. Hunter has completed many projects 

related to population health, health disparities, and immunization initiatives. 

 Grace Lee, MD, MPH is Board Certified in Pediatrics and Pediatric Infectious Diseases. She 

is the Director of the Center for Healthcare Research in Pediatrics (CHeRP) at Harvard 

Medical School where she has been conducting analyses for more than a decade on clinical 

and policy issues in immunization and infectious disease. She also is Associate Professor 

of Population Medicine and Pediatrics, Department of Population Medicine, Harvard Medical 

School, Boston, Massachusetts. She served on The Institute of Medicine (IOM) Committee 

on Review of Priorities in the National Vaccine Plan (NVP), and the IOM Board on 

Population Health and Public Health Practice. Dr. Lee also has participated extensively in 

activities related to immunization safety, including the Vaccine Safety Datalink (VSD) 

project. 

 Peter Szilagyi, MD, MPH is Board Certified in Pediatrics. He is Professor and Vice-Chair for 

Clinical Research in the Department of Pediatrics, David Geffen School of Medicine 

(DGSOM) at the University of California at Los Angeles (UCLA). He brings extensive 

experience as both an immunization delivery researcher and a primary care clinician. He 

has carried out a large body of work over more than 25 years dedicated to immunization 

practices and policies. He also is an expert on children’s health insurance plans. 

Before officially beginning the meeting, Dr. Bennett called the roll to determine whether any 

ACIP members had COIs. The following COIs were declared: 

 Robert Atmar receives research support from Takeda Vaccines 

 Dr. Belongia has a conflict for respiratory syncytial virus (RSV) due to receiving research 

support from Novavax 

 Dr. Romero has a conflict for RSV for funding non-related to vaccine trials and therapeutics 

 The remainder of the ACIP members declared no conflicts 

Dr. Bennett then requested that the liaison and ex officio members introduce themselves. A list 

of Members, Ex Officio Members, and Liaisons are included in the appendixes at this end of this 

document. 

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Advisory Committee on Immunization Practices (ACIP) 	 Summary Report October 19-20, 2016 

Hepatitis Vaccines 

Introduction 

José Romero, MD, FAAP, FIDSA, FPIDS 

ACIP Hepatitis Work Group Member 

Dr. Romero reminded everyone that the ACIP Hepatitis Work Group (WG) Terms of Reference 

are to: 

 Update ACIP recommendations for hepatitis B (HepB) vaccine: 

 Current ACIP recommendations 

• ACIP Routine Recommendation for HepB vaccine (Infants/Children). MMWR 

2005 Dec 23;54(RR-16):1-33. 

• ACIP Routine Recommendation for HepB vaccine (Adult). MMWR 2006 Dec 

8;55(RR-16):1-33. 

• Use of HepB vaccine for adults with diabetes mellitus: recommendations of 

the ACIP. MMWR 2011 Dec 23;60(50):1709-11. 

 Current CDC Guidelines 

• CDC guidance for evaluating health-care personnel for HepB virus (HBV) 

protection and for administering postexposure management. MMWR 2013 

Dec 20;62(RR-10):1-19. 

• Update: Shortened Interval for Postvaccination Serologic Testing of Infants 

Born to HepB-Infected Mothers. MMWR 2015 Oct 9;64(39):1118-20. 

The objectives for this session were to: 1) vote on removing the permissive language for the 

HBV birth dose to be administered after hospital discharge; and 2) vote to approve the revised 

HBV statement. 

From February through September 2016, the WG deliberated on HepB vaccine 

recommendation topics and held five teleconference meetings. The WG and ACIP members 

reviewed and commented on a draft of the statement prior to the ACIP’s October 2016 meeting. 

The key updates to the HepB vaccine recommendations include the following: 

 Removal of permissive language for delaying birth dose 

 Provide examples of chronic liver disease (CLD), including recommending HepB vaccine for 

persons with hepatitis C virus (HCV) infection 

 Postvaccination serologic testing for infants whose mother’s hepatitis B surface antigen 

(HBsAg) status remains unknown indefinitely 

 Testing HBsAg-positive pregnant women for HBV deoxyribonucleic acid (DNA) 

 Guidance on the use of maternal antiviral therapy during pregnancy 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Updated Hepatitis B Vaccine Recommendations 

Sarah Schillie, MD, MPH, MBA 

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

Centers for Disease Control and Prevention 

Dr. Schillie discussed Hepatitis B Virus (HBV) background, epidemiology, and prevention; 

existing HepB recommendations; and the revisions deliberated by the WG. The Hepatitis WG 

has drafted a revised statement for HepB vaccine recommendations. The revised statement is 

a single document containing guidance for HepB vaccination of infants, children, adolescents, 

and adults; testing of pregnant women for hepatitis B surface antigen (HBsAg), and, if positive, 

HBV DNA; HepB pre-vaccination and post-vaccination serologic testing; and HBV postexposure prophylaxis for occupational and non-occupational exposures. The revised statement 

incorporates previously-published recommendations from ACIP and CDC, and is augmented 

with the American Association for the Study of Liver Diseases (AASLD) recommendation 8A: 

The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of hepatitis B 

in HBsAg-positive pregnant women with an HBV DNA level >200,000 IU/mL [Terrault et al. 

Hepatology 2015]. 

The single revised statement will update the two existing ACIP HepB statements for infants, 

children and adolescents published in 2005 and for adults published in 2006. The revised 

statement also will incorporate previous ACIP guidance for HepB vaccination of adults with 

diabetes published in 2011, ensuring HBV protection among healthcare personnel (HCP) 

published in 2013, and CDC guidance for shortening the interval for post-vaccination serologic 

testing for infants born to HBsAg-positive mothers published in 2015. 

HBV is transmitted through percutaneous or mucosal exposure to infectious blood or body 

fluids. The virus is highly infectious and remains viable on environmental surfaces for at least 7 

days. HBV can be transmitted in the absence of visible blood [Bond et al. Lancet 1981]. 

Approximately 3,000 cases of acute HBV were reported to CDC in 2014, accounting for an 

estimated 19,200 new cases when considering under-ascertainment and underreporting. It also 

is estimated that 952 perinatal HBV infections occur annually. According to analyses from the 

National Health and Nutrition Examination Survey (NHANES), approximately 850,000 persons 

in the US have chronic HBV infection. Other studies have yielded higher estimates. Persons 

with chronic infection serve as the main reservoir for transmission. Imported chronic HBV 

accounts for approximately 95% of new cases in the US [National Notifiable Diseases 

Surveillance System (NNDSS); Ko et al. JPIDS 2016; Roberts et al. Hepatology 2016; Mitchell 

et al. PLoS One 2011]. 

The rate of reported acute HBV infections has declined by 90.6% since recommendations for 

HepB vaccine were first issued in 1982. The rate has been fairly stable from 2010-2014, 

although increases occurred in some populations such as white persons 30 through 39 years of 

age reporting injection drug use in Kentucky, Tennessee, and West Virginia [NNDSS; Harris et 

al. MMWR 2016]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

This graphic depicts the decline of acute HBV since 2000. Note that the rate is lowest for 

persons 19 years of age and younger, which is likely the result of routine vaccination: 

Chronic HBV infection develops in approximately 90% of infected infants, 30% of infected 

children less than 5 years of age, and in less than 5% of infected persons 5 years of age and 

older. The risk of premature death from cirrhosis or liver cancer with chronic HBV infection is 

approximately 25% if infected during childhood, and approximately 15% if infected after 

childhood [Mast et al. MMWR 2005; Goldstein et al. Int J Epidemiol 2005]. 

Perinatal transmission occurs primarily from mucosal exposure to infected blood and other body 

fluids during delivery. Without post-exposure prophylaxis (PEP), perinatal HBV infection 

develops in approximately 90% of infants born to mothers who are HBsAg-positive and hepatitis 

B e antigen (HBeAg)-positive, and 5% to 20% of infants born to mothers who are HBsAgpositive and HBeAg-negative [Nelson et al. JPIDS 2014; Mast et al. MMWR 2005]. 

The WHO recommends all infants receive their first dose of HepB vaccine as soon as possible 

after birth, preferably within 24 hours [WHO Hepatitis B Vaccines Position Paper. Weekly 

Epidemiological Record 2009]. Countries in which a HepB birth dose (HepB-BD) vaccine has 

been implemented in the national immunization program are depicted in the following map in 

green, reflecting 49% of countries: 

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To identify HBV infected pregnant women, all women should be tested routinely for HBsAg 

during pregnancy during an early prenatal visit. Testing should occur during every pregnancy, 

even if the woman has been previously vaccinated or tested. For infants born to HBsAgpositive mothers, ACIP recommends HepB vaccine and HBIG within 12 hours of birth. For 

those infants with birthweights <2000 grams, the birth dose is not counted as part of the vaccine 

series. Infants born to mothers with unknown HBsAg weighing ≥2000 grams should receive 

HepB vaccine within 12 hours of birth. Infants weighing <2000 grams should receive both HepB 

vaccine and HBIG within 12 hours of birth. For those infants weighing <2000 grams, the birth 

dose is not counted as part of the vaccine series. Infants weighing ≥2000 grams who are born 

to HBsAg-negative mothers should receive HepB vaccine before hospital discharge. For infants 

weighing <2000 grams born to HBsAg-negative mothers, the first dose of HepB vaccine should 

be delayed until 1 month of age or hospital discharge. 

The existing recommendations contain permissive language to delay the birth dose. The 

language states that, “On a case-by-case basis and only in rare circumstances, the first dose 

may be delayed until after hospital discharge for an infant who weighs ≥2,000 grams and whose 

mother is HBsAg-negative.” A physician’s order to withhold the birth dose should be present, 

along with a copy of the original maternal HBsAg-negative laboratory report. The birth dose 

should be administered by 2 months of age, and should not be delayed in high risk situations, 

such as high risk maternal behavior or expected poor compliance with follow-up. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

PEP shortly after birth is efficacious in preventing perinatal HBV transmission. HepB vaccine 

alone is 75% effective in preventing perinatal HBV transmission, and HepB immune globulin 

(HBIG) alone 71% effective. The combined efficacy is 94% [Beasley et al. Lancet 1983; Lee et 

al. BMJ 2006]. 

Serologic evidence of vaccine-induced protection is assessed by the level of antibody to 

hepatitis B surface antigen (anti-HBs) measured 1 to 2 months after HepB vaccination. AntiHBs of ≥10mIU/mL corresponds to vaccine-induced protection. Protection exists for 30 years or 

longer among immunocompetent vaccine responders [Leuridan et al. CID 2011; Bruce et al. 

JID 2016]. 

The 3-dose vaccine series results in protective anti-HBs in 98% of healthy infants and 90% to 

95% of healthy children and adults aged 40 years and younger. Lower seroprotection is 

associated with prematurity, advanced age, diabetes, obesity, chronic illness, and smoking 

[Schillie et al. Vaccine 2012; Mast et al. MMWR 2006]. 

Anti-HBs after the HepB vaccine series wanes over time. However, even when levels wane to 

less than <10 mIU/mL, breakthrough HBV infections are uncommon in immunocompetent 

vaccine responders [Middleman et al. Pediatrics 2014; Leuridan et al. CID 2011]. 

In terms of existing HepB recommendations, the national strategy to eliminate HBV 

transmission in the US encompasses the following: 1) screen all pregnant women for HBsAg 

and provide prophylaxis consisting of HepB vaccine and HBIG within 12 hours of birth for all 

infants born to HBsAg-positive women; 2) universal vaccination of all infants beginning at birth, 

before hospital discharge, as a safety net; 3) routine vaccination of previously unvaccinated 

children and adolescents aged 19 years and less; and 4) vaccination of adults at risk for HBV 

infection, including those requesting protection from HBV without acknowledgment of a specific 

risk factor [Mast et al. MMWR 2005; Mast et al. MMWR 2006]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

The HepB vaccine series is completed at age 6 months for infants born to HBsAg-positive or 

unknown mothers, or at age 6 to 18 months for infants born to HBsAg-negative mothers. Postvaccination serologic testing consisting of testing for anti-HBs and HBsAg is recommended at 

age 9 to 12 months, or 1 to 2 months after the final dose of the vaccine series if delayed, for 

infants born to HBsAg-positive mothers. Three-dose revaccination followed by repeat postvaccination serologic testing is recommended for infants with anti-HBs <10mIU/mL. HepB 

vaccination is recommended for all children and adolescents aged <19 years. Those not 

previously vaccinated should be vaccinated routinely at any age using an appropriate dose and 

schedule. 

Adults recommended for HepB vaccination include those at high risk for infection by sexual 

exposure, such as sex partners of HBsAg-positive persons and men who have sex with men 

(MSM); those at risk for infection by percutaneous or mucosal exposure to blood, such as 

injection-drug users, health-care and public safety workers, persons with end-stage renal 

disease, and adults with diabetes; international travelers to regions with high or intermediate 

HBV endemicity, defined as HBsAg-positive prevalence ≥8% and ≥2%, respectively; persons 

with chronic liver disease; persons with HIV infection; and all persons seeking protection from 

HBV infection even without acknowledgement of a specific risk factor. All adults in certain 

settings also are recommended for HepB vaccination, including the following: 

 Sexually transmitted disease treatment facilities 

 HIV testing and treatment facilities 

 Facilities providing drug-abuse treatment and prevention services 

 Health-care settings targeting services to injection-drug users 

 Correctional facilities 

 Health-care settings targeting services to men who have sex with men 

 Chronic-hemodialysis facilities and end-stage renal disease programs 

 Institutions and nonresidential day care facilities for developmentally disabled persons 

Vaccination of persons who are immune to HBV infection due to past infection or vaccination 

does not increase risk for adverse events (AEs). However, pre-vaccination serologic testing 

might reduce costs by avoiding vaccination of persons who already are immune. Prevaccination serologic testing is recommended for household, needle-sharing, or sex contacts of 

HBsAg-positive persons; persons born in regions of high HBV endemicity; and HIV-positive 

persons. The existing recommendations also state that pre-vaccination serologic testing might 

be cost-effective for injection drug users, incarcerated persons, MSM, and persons born in 

regions of intermediate HBV endemicity. The first vaccine dose typically should be 

administered immediately after the collection of blood for serologic testing. 

Post-vaccination serologic testing for immunity is not recommended after routine vaccination of 

infants, children, adolescents, and adults. Post-vaccination serologic testing is recommended 

for infants born to HBsAg-positive mothers, HCP, chronic hemodialysis patients, HIV-infected 

and other immunocompromised persons, and sex partners of HBsAg-positive persons. Testing 

is recommended 1 to 2 months after the final dose of the vaccine series or at age 9 to 12 

months for infants of HBsAg-positive mothers. Revaccination is recommended if anti-HBs is 

<10 mIU/mL. 

In terms of post-exposure prophylaxis following occupational exposures, unvaccinated HCP 

exposed to blood or body fluids from a source patient positive for HBsAg should receive 1 dose 

of HBIG and initiate vaccination. Those exposed to a source patient negative for HBsAg should 

initiate vaccination. A previously vaccinated HCP who is a known vaccine responder requires 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

no PEP regardless of source patient status. Previously vaccinated HCP who are known nonresponders after 3 vaccine doses and exposed to a positive source patient should receive 1 

dose of HBIG and initiate revaccination. Those exposed to a source patient negative for HBsAg 

should initiate revaccination. Previously vaccinated HCP who are known non-responders after 

6 vaccine doses and exposed to a positive source patient should receive 2 doses of HBIG 

separated by 1 month. Those exposed to a source patient negative for HBsAg require no 

prophylaxis. 

With regard to post-exposure recommendations following non-occupational exposures, an 

unvaccinated person exposed to a HBsAg-positive source should receive a HepB vaccine 

series and HBIG. A previously vaccinated person exposed to a HBsAg-positive source should 

receive a dose of HepB vaccine. An unvaccinated person exposed to a source with an 

unknown HBsAg status should receive the HepB vaccine series, while a vaccinated person 

exposed to a source with unknown status requires no prophylaxis. 

Dr. Schillie then discussed the revisions to the recommendations deliberated upon by the WG. 

The WG deliberated upon and supports guidance for testing HBsAg-positive pregnant women 

for HBV DNA. DNA testing identifies infants at greatest risk for perinatal HBV infection and 

prioritizes women for referral for antiviral therapy in accordance with AASLD’s suggestion for 

maternal antiviral therapy to reduce the risk of perinatal transmission when maternal HBV DNA 

is >200,000 IU/mL. 

The WG also deliberated upon and supports guidance for post-vaccination serologic testing for 

infants whose mother’s HBsAg status remains unknown indefinitely, such as infants 

surrendered anonymously shortly after birth. Note that all 50 states have some form of safehaven law to reduce the risk of infant abandonment, and that medical data on these infants is 

lacking. 

The WG also deliberated on removal of the permissive language for birth dose administration 

after hospital discharge. The following table reflects the existing and proposed language. Note 

the proposed revised language on the right, which reflects removal of the permissive paragraph 

from the existing language regarding delaying birth dose administration: 

Existing Language 

For all medically stable infants weighing 

≥2,000 grams at birth and born to HBsAgnegative mothers, the first dose of vaccine 

should be administered before hospital 

discharge. Only single-antigen HepB vaccine 

should be used for the birth dose. 

On a case-by-case basis and only in rare 

circumstances, the first dose may be delayed 

until after hospital discharge for an infant who 

weighs ≥2,000 grams and whose mother is 

HBsAg-negative. 

Revised Language (proposed) 

For all medically stable infants weighing 

≥2,000 grams at birth and born to HBsAgnegative mothers, the first dose of vaccine 

should be administered before hospital 

discharge. Only single-antigen HepB vaccine 

should be used for the birth dose. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Included in the WG’s deliberations was a study demonstrating an increase in HBV infections for 

infants born to HBsAg-positive mothers with increasing age at first dose of vaccination. The 

adjusted odds ratio for an increase in infection was 4.3 (95% CI, 2.2-8.4) [Marion et al. Am J 

Epidemiol 1994]. Birth dose coverage in the US is currently 72.4% and has remained relatively 

stable in recent years. Note that current coverage is below the Healthy People 2020 target of 

85%. 

The WG also discussed the safety net provided by birth dose prior to hospital discharge, 

including when infants born to infected mothers are not identified due to errors in maternal 

HBsAg testing or transcription or reporting of test results. Note that the WG did not reach 

consensus on removal of the permissive language. 

The WG deliberated upon and supports providing examples of chronic liver disease (CLD) in the 

statement. The existing guidance recommends HepB vaccination for persons with CLD. The 

WG supports providing examples of CLD such as cirrhosis, fatty liver disease, alcoholic liver 

disease, autoimmune hepatitis, and liver function tests >2 times the upper limit of normal. 

Three-dose HepB vaccine coverage among adults aged ≥19 years with chronic liver conditions 

is slightly less than 30% [Williams et al. MMWR 2016]. 

CDC supports explicit language for recommending HepB vaccination for persons with HCV 

infection. The increasing incidence of HBV and HCV infections have been noted in young, nonurban adults who inject drugs in Kentucky, Tennessee, and West Virginia. Concurrent HepB 

virus infection may increase the risk for liver disease progression among HCV-infected persons 

[Zibbell et al. MMWR 2015; Harris et al. MMWR 2016; Bell et al. Acta Gastroenterol Belg 

2000.; Oh et al. BMC Cancer 2012]. 

For discussion and vote, Dr. Schillie posed the following questions: 

 Does ACIP approve removing the permissive language for the HepB vaccine birth dose to 

be administered after hospital discharge? 

 Does ACIP approve the revised HepB statement? 

Discussion Points 

Dr. Belongia requested insight as to why the original language was included regarding the 

permissive birth dose prior to discharge, and an example of what would be a circumstance that 

would have been considered reasonable not to vaccinate prior to hospital discharge. 

Dr. Schillie replied that she had no insight as to why the language originally was placed in the 

recommendation. That was from the 2005 recommendations. Some of the WG deliberations in 

favor of not removing the permissive language was for mothers who feel that they know that 

they are negative for HBV, and that perhaps those mothers should not be required to have their 

infant vaccinated before hospital discharge. Perhaps they should have the choice to have the 

infant vaccinated later in life. 

Dr. Hunter asked whether there were any data that would suggest that removing the birth dose 

permissive recommendation would change the overall completion rate of the 3-dose infant 

series and, if not, whether there were any plans to study this question. 

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Dr. Schillie responded that there are studies which are 10 to 15 years old that showed an 

association with receipt of the birth dose and timely completion of the vaccine series. 

Speaking on behalf of some mothers she has spoken to about the birth dose, Dr. Even (ACHA) 

reported that these mothers have concern about vaccinating a child at birth in terms of their 

immune system not being ready for vaccine, and that the infant’s immune system should be 

more mature before beginning vaccination. 

While they may have concerns, Dr. Moore said she did not believe there was any scientific 

evidence to support that. She reminded everyone that having a clear recommendation does not 

mandate anything. People make their own choices all of the time about whether to refuse 

something that is recommended. It did not seem to her that removal of the permissive language 

would result in a compulsion of parents to immunize who are resistant to that any more than any 

other recommendation does. However, in her experience, clinicians may choose to have a 

patient get their vaccine at the doctor’s office at the 2-week visit. That may be for convenience 

for the clinicians, and so that the clinician is paid for that visit instead of it being something that 

the hospital takes care of. Other issues may come into play in terms of pediatric practice. A 

clear recommendation without the permissive language may make it easier to make vaccination 

routine in hospitals prior to discharge. 

Regarding the recommendation for infants <2000 grams born to seronegative mothers, Dr. 

Walter pointed out that the language stated “delay dose of HepB vaccine until age 1 month or 

hospital discharge.” He asked what the intent was, especially for a child who is approximately 

2000 grams or just under that who may be discharged at 2 to 3 weeks of age. 

Dr. Schillie replied that among term infants, vaccine response is normal when it is administered 

early in life. Vaccine response among low birthweight infants improves quite a bit when 

vaccination is delayed until about 1 month of life. When low birthweight babies are immunized 

in the first couple of days of life, 60% to 65% might achieve seroprotective antibody levels. 

When vaccination in those infants is delayed starting at 1 month of life, 90% or more achieve 

seroprotective levels. 

Dr. Walter asked whether they should be vaccinated at 1 month or at hospital discharge, which 

may be before 1 month. The language is somewhat confusing. 

Dr. Schillie clarified that the language shown on the slide was taken verbatim from the existing 

recommendation, which do not specify a preference. It states either “1 month of life or hospital 

discharge.” The WG could certainly entertain a preference. 

Regarding testing post-vaccination for infants born to HBsAg-positive mothers, Dr. Kimberlain 

(AAP) noted that one of Dr. Schillie’s slides illustrated that the recommendation is 9 to 12 

months or 1 to 2 months of the final dose of the vaccine series. Pointing out that it used to be 9 

to 18 months, he asked whether Dr. Schillie could comment on why it changed from 18 to 12 

months. 

Dr. Schillie indicated that in 2015, CDC issued a recommendation to shorten that interval from 9 

to 18 months to 9 to 12 months for two reasons. One, there were new data that showed the 

decline in anti-HBs over time when post-vaccination testing was done at increasing intervals 

following vaccination. Infants were falsely identified as non-responders and were being 

revaccinated unnecessarily due to the decline in anti-HBs over time. Second, COMVAX® 

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production was discontinued. With COMVAX®, the last dose was given at age 15 months. So, 

one reason the interval was extended out to 18 months was to accommodate intervals 

completing vaccination with COMVAX®. 

Dr. Schaffner (NFID) said he was supportive of removing the permissive language regarding the 

HepB birth dose. He requested a brief discussion of adult immunization, because he was 

disappointed in the WG’s report because he thought an opportunity had been missed. Part of 

the title of the document is “A Strategy to Interrupt Transmission.” As was demonstrated, there 

have been flat rats in the adult population for some time. Indeed, rates are increasing in some 

parts of the country in some age groups. This is an opportunity to move forward in the strategy 

to interrupt transmission in a more innovative and assertive way. After the 19th birthday, in a 

way that differs from all other vaccine recommendations, an adult has to acquire risk before 

being eligible for immunization. However, individuals do not have to wait to be exposed to 

measles before receiving measles vaccine. Also, it is known that this risk-based strategy is 

honored most often in the breech rather than the observance. Therefore, it is a strategy that is 

stuck or even failed. It has been about 15 years since universal immunization has been 

recommended of everyone up to the 19th birthday. He has never understood why, once 

someone turns 19 years of age plus one day, they are no longer eligible. He suggested taking 

that universal recommendation with that cohort and moving it forward with them. This is an 

opportunity to move universal immunization up to age 35, 40, 50. That would be innovative and 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Kimberlain (AAP) pointed out that the 2015 STI guidelines do not specifically state this, but 

points to the 2005 Morbidity and Mortality Weekly Report (MMWR), not the 2015 document. If 

there is a living document with the STI guidelines, he suggested that it might be worth adding 

that in. 

Dr. Messonnier asked whether COID has language pertaining to this in the Red Book, and if 

there is an opinion and / or agreement about the permissive language. 

Dr. Maldonado (AAP) replied that COID discussed this on a conference call the previous week, 

and was in agreement with the recommendation. Discussion regarding the 2005 

recommendations pertained to the difficulty among practitioners and hospitals in developing a 

birth dose within their systems and capturing every child. The idea was to allow some 

permissiveness. Since that point, most hospitals and practices have been able to make that 

switch. 

Dr. Kimberlain (AAP) added that the Red Book currently contains permissive language, but they 

are working actively on the 2018 edition and would be delighted to incorporate this in should 

ACIP vote in favor of removing the permissive language. 

Dr. Thompson (NVAC) asked what is known about the fraction of births that occur outside of 

what would be captured as hospitals in terms of whether a small part of the population is being 

missed who might be relevant to uptake, and what is being done to improve uptake. 

Dr. Schillie replied that while the WG focused primarily on infants born in the hospital, certainly 

they are concerned about those born outside the hospital as well. However, she said she did 

not have data on the proportion of infants born outside of hospitals and their HepB birth dose 

coverage rates. In terms of what is being done to improve rates of birth dose before discharge, 

educational efforts are underway to try to educate mothers and providers about the importance 

of the birth dose as a safety net. Birth dose coverage before hospital discharge also is a quality 

metric for hospitals that choose to use that measure. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

strategic rather than lethargic. He urged the colleagues to re-deliberate and do something 

innovative regarding this continuing concern about HepB acutely occurring in adult age groups. 

Dr. Schillie thought Dr. Schaffner raised an excellent point. Certainly, there are areas in which 

HBV is increasing among young adult populations such that immunization of adults 30 through 

39 years of age would help to address the increasing HBV prevalence among those 

populations. 

Dr. Wexler (Immunization Action Coalition) pointed out that the permissive language was 

developed as restrictive language. She has been attending ACIP meetings since before 2000, 

and she has been following the HepB birth dose issue since 1991. She recalled that before the 

thimerosal controversy, there were very high rates of HepB vaccination at birth. The rate was 

approaching 80%, decreased to zero with thimerosal, and then increased only to about 40% 

after the 1998 thimerosal fiasco. In 2002, ACIP recommended the birth dose for every baby. 

Rates began to increase again, but not very quickly. The purpose of the language in 2005 

being referred to as “permissive” that actually was “restrictive” was to say, “Do not give the birth 

dose later. Give it at birth, except in rare circumstances and on a case-by-case basis.” As a 

result of that, the birth dose rate has been increasing gradually and is approximately 72%. That 

is within 3 days of birth, not before hospital discharge. Dr. Wexler emphasized that she wanted 

to set the stage for how important it is to give this birth dose in the hospital. She said she had 

just received an email from a Perinatal HepB Coordinator who has been to every hospital in her 

state, and is fighting to get the birth dose implemented. Private doctors are still delaying the 

dose and giving it in their practices at the 1-week visit. She is hungry for help about what to do. 

In light of the former restrictive language and perhaps moving toward the language of everybody 

giving the vaccine, programmatically it would be very helpful to Perinatal HepB Coordinators for 

ACIP to explain what it means to administer the dose before hospital discharge—either before 

12 hours of age or before 24 hours of age. That would help Perinatal HepB Coordinators and 

everyone else be very clear in what they are trying to implement rather than stating “before 

hospital discharge.” 

Dr. Decker (Sanofi Pasteur) added that another factor which played into this that Dr. Wexler did 

not mention, which was an economic / political issue. At the time, there was the original 

recommendation and hospitals adopted it widely. When the thimerosal issue arose, hospitals 

leapt at the opportunity to keep this out of their programs because it was an unfunded mandate. 

When it occurs during the birth process, it was capitated for the mother but nobody was paying 

for the injection to the baby. Another reason there was the language in 2005 was because it 

was part of political compromise. This is 11 years later and in order to make progress, it is 

necessary to move to mandatory language. He agreed that rather than stating “before 

discharge” they should state “within the first 24 hours of life.” He emphasized that they must be 

very specific and concrete if they wanted to get it done. 

Dr. Fryhofer (AMA / ACP) noted that on page 5 of the handout in terms of adults recommended 

for HepB vaccine, an example was not given for the bullet “persons at risk for infection by 

sexual exposure” through having more than one sex partner within the last six months. This 

relates to what Dr. Schaffner was saying. Even patients in their 50s, 60s, and up may 

experience changes in their situations and that may apply to them. She applauded the WG for 

highlighting fatty liver as an indication as an example of CLD, because an increasing number of 

patients with fatty liver are being seen in practices because of the obesity crisis. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Hunter asked why the cutoff for the upper limit of normal of liver function tests as a risk was 

twice the upper limit of normal versus three times the upper limit of normal, which is what most 

clinicians use as a decision factor in clinical situations. 

Dr. Schillie replied that the number was chosen fairly arbitrarily. There are some clinical 

guidelines that use greater than two times the upper limit of normal in some of the decision 

factors. Unrelatedly, an algorithm for prenatal testing was issued that received some comments 

that the alanine aminotransferase (ALT) cutoff was perhaps too low. It is important to capture a 

level that is not too high or too low, and the WG is open for feedback on that level. 

Dr. Hunter added that for primary care physicians, he was arguing in general to try to make the 

recommendations as uniform as possible for correct implementation. 

Dr. O’Leary (PIDS) noted that the 2005 guidelines have fairly extensive guidance for hospitals 

on policies to increase the uptake of the birth dose, screening, et cetera, and included 

recommending the use of standing orders. He wondered whether that would be included in the 

new guidelines. Dr. Schillie replied that it would. 

Regarding Dr. Schaffner’s comments, Dr. Ward (Director, Division of Viral Hepatitis) noted that 

the major gap in HepB coverage is among adults. That is where most cases are being 

observed in states such as Tennessee, which is heavily related to the opioid abuse crisis and 

the injection of those medications or heroin. There has been an elimination goal, although it is 

one that has been proposed without a numerical target, since the infant vaccine was 

recommended by ACIP in about 1992. This elimination target has taken on some renewed 

interest. The IOM, now known as the National Academy of Medicine (NAM), has convened a 

panel to set elimination targets for HepB and HepC elimination and is framing it as the 

elimination of HepB transmission and disease as a public health threat in the US. This is 

proposed to be coming out from that panel in Spring 2017. A more ambitious HepB vaccination 

policy for the most vulnerable parts of the population, in this case young, middle-aged, and even 

older adults, would be very appropriate. He suggested that the WG could reconvene to assess 

stronger recommendations for adults, while still hopefully having ACIP agree with what already 

was before them during this session. 

Regarding measurement, Dr. Lee pointed out that it would be helpful to understand whether the 

rate of 72% for the birth dose excludes premature populations. That is, if 10% actually are 

premature, vaccination rates may be higher. It also might give them a better sense of where to 

target improvement efforts. From a systems level perspective, it seemed like they were trying to 

bridge the gaps and that minimizing permissive use would be helpful in that instance. It also 

might be helpful to assess the impact of alternative vaccination strategies, particularly in terms 

of the adult disease burden. She asked whether the WG would consider that. 

Dr. Moore completely supported the idea of having the WG consider an age-based 

recommendation for adults. As the Program Manager for Tennessee, she reported that they are 

one of the three states that are struggling mightily with this. Risk-based strategies have not 

helped them. Reminding everyone that the proposed language specified hospitals and 

excluded children born outside of the hospital setting, she emphasized that the concern was not 

about the setting. It was about protecting the infant at birth. She asked whether there would be 

opposition to proposing, especially from a programmatic standpoint, the clear-cut 

communication message that the first dose should be administered within 24 hours of life rather 

than before hospital discharge. That would eliminate the setting of the birth from consideration 

in the protection of the newborn. 

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Dr. Hunter indicated that the American Congress of Obstetricians and Gynecologists (ACOG) 

website reported that there are about 35,000 births per year outside of the hospital setting, 

which is about 0.9% of births. 

Dr. Belongia supported the suggested amendment of the inclusion of “within 24 hours of life” 

and elimination of setting, given that it does not matter whether the birth occurs in the hospital. 

Dr. Messonnier pointed out that the language “within 24 hours of birth” is consistent with the 

WHO. In order to facilitate the upcoming Vaccines for Children (VFC) vote, she requested that 

the specific language preferred be utilized in terms of “within 24 hours of birth” or “before 

hospital discharge.” 

Dr. Lee asked whether there were any implementation issues of concern with regard to the 

proposed change to “within 24 hours of birth” versus “before hospital discharge.” 

Dr. O’Leary (PIDS) said he would argue that the suggested change would make things clearer 

for hospitals and clinicians, because there is confusion regarding whether they should wait for 

72 hours if it is a Cesarean section (C-section) for example. 

Dr. Riley added that from a programmatic standpoint, it would just mean changing standing 

orders. She did not think this would be problematic. However, she was not wildly optimistic that 

people who deliver outside of the hospital suddenly will be the ones who get vaccinated. The 

very people who deliver outside of the hospital generally are not people who are tremendously 

excited about organized medicine, and the need to get vaccinated. 

Dr. Stephens emphasized the need to keep in mind Dr. Schaffner’s point about universal 

vaccination. 

Dr. Kempe reiterated the importance of the WG returning to the adult recommendations at a 

later time. 

Dr. Szilagyi agreed, stressing that risk-based strategies typically are not effective. 

In terms of implementation considerations, Patsy Stinchfield (NAPNAP) underscored that a lot 

of education will be needed for those who do not meet the 24-hour stipulation. For example, a 

birth center might ask, “We’re at hour 25. What do we do?” 

Christina Hildebrand (A Voice for Choice Advocacy) expressed concern about the 24 hours, 

pointing out that the US has the highest rate of infant mortality within the first day of birth and 

also is one of the few countries that has a HepB vaccine given within the first 24 hours of birth. 

She wondered whether CDC and / others have conducted research to assess this. It concerns 

her that there may be a correlation, and she requested that consideration be given to this before 

making that recommendation. 

Dr. Schillie replied that CDC continuously monitors the safety of HepB vaccine, including when 

administered shortly after birth. It is a very safe vaccine. Anaphylaxis occurs in about 1 out of a 

million cases, and CDC will continue to monitor this. There are data to support the safety of the 

vaccine being given so shortly after birth, including that it does not increase the work-up for 

sepsis in young infants. 

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14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

 

 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Riley noted that in addition to the safety data, it would be important to point out that most 

infant mortality in the US is in pre-term infants who are not the babies being vaccinated within 

the first 24 hours of life because they are <2000 grams. 

Vote: Hepatitis B Vaccine Birth Dose Amendment 

Dr. Romero made a motion to approve the advised recommendation as stated, “For all 

medically stable infants weighing ≥2,000 grams at birth and born to HBsAg-negative mothers, 

the first dose of vaccine should be administered before hospital discharge. Only single-antigen 

HepB vaccine should be used for the birth dose.” Dr. Atmar seconded the motion. Dr. Moore 

offered an amendment to the proposed language to replace the statement “before hospital 

discharge” with the statement “within 24 hours of birth.” Dr. Belongia seconded the suggested 

amendment. Dr. Bennett called for a vote on the amendment. The motion carried unanimously 

with 14 affirmative votes, 0 negative vote, and 0 abstentions. The disposition of the vote was as 

follows: 

0 Opposed: N/A 

0 Abstained: N/A 

Vote: Hepatitis B Vaccine Amended Birth Dose & Removal of Permissive Language 

Dr. Romero motioned to approve the overall birth dose recommendation as amended, “For all 

medically stable infants weighing ≥2,000 grams at birth and born to HBsAg-negative mothers, 

the first dose of vaccine should be administered within 24 hours of birth. Only single-antigen 

HepB vaccine should be used for the birth dose” and to remove the permissive language 

reading “On a case-by-case basis and only in rare circumstances, the first dose may be delayed 

until after hospital discharge for an infant who weighs ≥2,000 grams and whose mother is 

HBsAg-negative.” Dr. Atmar seconded the motion. The motion carried unanimously with 14 

affirmative votes, 0 negative vote, and 0 abstentions. The disposition of the vote was as 

follows: 

0 Opposed: N/A 

0 Abstained: N/A 

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0 Opposed: N/A 

 0 Abstained: N/A 

Single antigen vaccine Single-antigen1 and combination vaccine2,3 

Birth Maternal HBsAg Dose Age Dose Age 

weight status 

≥2000 g Positive 1 Birth (≤12 hrs)1 1 Birth (≤12 hrs )1 

2 1-2 months 2 2 months 

3 6 months 3 4 months 

4 6 months 

Unknown 1 Birth (≤12 hrs)1 1 Birth (≤12 hrs)1 

2 1-2 months 2 2 months 

3 6 months 3 4 months 

4 6 months 

Negative 1 Birth (before discharge)1 1 Birth (before discharge)1 

2 1-2 months 2 2 months 

3 6 -18 months 3 4 months 

4 6 months 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Vote: Hepatitis B Vaccine Overall Recommendations 

Dr. Romero motioned to approve the overall recommendations for Hepatitis B vaccination. Dr. 

Atmar seconded the motion. The motion carried unanimously with 14 affirmative votes, 0 

negative vote, and 0 abstentions. The disposition of the vote was as follows: 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

VFC Resolution 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Santoli indicated that the purpose of this resolution was to align the VFC resolution with the 

ACIP’s updated HepB recommendations. The eligible groups for this resolution are all children 

and adolescents birth through 18 years of age. The tables below list the acceptable vaccination 

schedules for children and adolescents birth through 18 years of age, which are directly from 

the draft of the recommendations that ACIP has reviewed, discussed, and approved. The 

change will be made that was just discussed and voted upon, such that “birth” is replaced with 

“within 24 hours” through all parts of the tables: 

Table 1, Part I: Infants 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Table 1, Part 2: Infants 

<2000 g Positive 1 Birth (≤12 hrs)1 1 Birth (≤12 hrs)1 

2 1 month 2 2 months 

3 2-3 months 3 4 months 

4 6 months 4 6 months 

Unknown 1 Birth (≤12 hrs)1 1 Birth (≤12 hrs)1 

2 1 month 2 2 months

3 2-3 months 3 4 months 

4 6 months 4 6 months 

Negative 1 1 

2 2 months 2 2 months 

3 6 -18 months 3 4 months 

4 6 months 

Table Notes: 

1. Only a single antigen hepatitis B vaccine (ENGERIX-B® or RECOMBIVAX HB®) can be given at birth. 

2. Pediarix® [DTaP-IPV-HepB] is licensed for children 6 weeks through 6 years of age. 

3. Use of brand names is not meant to preclude the use of other comparable US licensed vaccines. 

Table 2: Children and Adolescents 

Age Schedule1, 6 

Children (1 through10 years) 0, 1, and 6 months2  

0, 2, and 4 months2 

0, 1, 2, and 12 months2,4 

Adolescents (11 through 18 years) 0, 1, and 6 months2 

0, 1, and 4 months2 

0, 2, and 4 months2 

0, 12, and 24 months2 

0 and 4-6 months3 

0, 1, 2, and 12 months2,4 

0, 7 days, 21-30 days, 12 months5 

Table Notes 

1. Children and adolescents may be vaccinated according to any of the schedules indicated, except as noted. Selection of a 

schedule should consider the need to optimize compliance with vaccination. 

2. Pediatric/adolescent formulation. 

3. A two-dose schedule of Recombivax-HB Adult Formulation is (10 micrograms) is licensed for adolescents aged 11 through 15 

years. When scheduled to receive the second dose, adolescents aged > 15 years should be switched to a three-dose series, with 

doses 2 and 3 consisting of the pediatric formulation administered on an appropriate schedule. 

4. A four-dose schedule of Engerix B® is licensed for all age groups. 

5. Twinrix® can be administered to persons 18 years of age before travel or any other potential exposure on an accelerated 

schedule at 0, 7, and 21-30 days, followed by a dose at 12 months. 

6. Use of brand names is not meant to preclude the use of other comparable US licensed vaccines. 

The only items to be added to Table 2 will be at the bottom of the Adolescent part of the table, 

which is the accelerated schedule that can be used when administering Twinrix®. This does 

apply to 18 year olds who are covered by the VFC program. 

There also is information about interrupted schedules and minimum dosing schedules that 

comes from the current version of the recommendations that was voted on and approved, as 

well as prior versions of the recommendations: 

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Age 1 month or at hospital 

discharge1 

Age 1 months or at hospital 

discharge1 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Interrupted Schedules and Minimum Dosing Intervals 

 When the HepB vaccine schedule is interrupted, the vaccine series does not need to be 

restarted. If the series is interrupted after the first dose, the second dose should be 

administered as soon as possible, and the second and third doses should be separated by 

an interval of at least eight weeks. If only the third dose has been delayed, it should be 

administered as soon as possible. 

 The third dose of vaccine must be administered at least eight weeks after the second dose 

and should follow the first dose by at least 16 weeks; the minimum interval between the first 

and second doses is four weeks. Inadequate doses of hepatitis B vaccine or doses received 

after a shorter-than-recommended dosing interval should be re-administered, using the 

correct dosage or schedule. 

 Vaccine doses administered ≤4 days before the minimum interval or age are considered 

valid. Because of the unique accelerated schedule for Twinrix®, the four-day guideline does 

not apply to the first three doses of this vaccine when administered on a 0 day, 7 day, 21-30 

day, and 12 month schedule. 

 In infants, administration of the final dose is not recommended before age 24 weeks (164 

days). 

There also is guidance about revaccination to make sure those doses are included in the VFC 

program, which is taken directly out of the statement in various categories for which 

revaccination would be recommended: 

Revaccination 

Revaccination (i.e., booster dose, challenge dose, or revaccination with a complete series) is 

not generally recommended for persons with a normal immune status who were vaccinated as 

infants, children, or adolescents. Revaccination when anti-HBs is <10 mIU/mL is recommended 

for the following: 

 Infants born to HBsAg-positive mothers. HBsAg-negative infants with anti-HBs <10 mIU/mL 

should be revaccinated with a second three-dose series and retested (HBsAg and anti-HBs) 

1-2 months after the final dose of vaccine. 

 Hemodialysis patients. For hemodialysis patients, the need for booster doses should be 

assessed by annual anti-HBs testing. A booster dose should be administered when antiHBs levels decline to <10 mIU/mL. 

 Other immunocompromised persons. For other immunocompromised persons (e.g., HIVinfected persons, hematopoietic stem-cell transplant recipients, and persons receiving 

chemotherapy), the need for booster doses has not been determined. When anti-HBs levels 

decline to <10 mIU/mL, annual anti-HBs testing and booster doses should be considered for 

persons with an ongoing risk for exposure. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

 Persons with postvaccination serologic testing results that do not demonstrate protection. 

This includes children and adolescents through age 18 years who are chronic hemodialysis 

patients, HIV-infected, otherwise immunocompromised (e.g., hematopoietic stem-cell 

transplant recipients or persons receiving chemotherapy), or sex partners of HBsAg-positive 

persons. Persons in these groups found to have anti-HBs concentrations of <10 mIU/mL 

after the primary vaccine series should be revaccinated. 

Recommended Dosage 

Refer to product package inserts. 

Contraindications and Precautions 

Contraindications and Precautions can be found in the package inserts available at 

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM093833 

Statement Regarding Update Based on Published Documents 

[If an ACIP recommendation regarding Hepatitis B vaccination is published within 12 months 

following this resolution, the relevant language above (except in the eligible groups sections) will 

be replaced with the language in the recommendation and incorporated by reference to the 

publication URL.] 

Vote: VFC Resolution for Hepatitis B Vaccine Recommendations 

Dr. Stephens motioned to approve the VFC Resolution for the Hepatitis B Vaccine 

Recommendations. Dr. Romero seconded the motion. The motion carried unanimously with 14 

affirmative votes, 0 negative vote, and 0 abstentions. The disposition of the vote was as 

follows: 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

0 Opposed: N/A 

0 Abstained: N/A 

Pertussis 

Introduction 

Laura Riley, MD 

ACIP Pertussis Vaccine Work Group 

Dr. Riley reminded everyone of the following terms of reference for the Pertussis Vaccine WG, 

indicating that only the first term of reference remained to be completed, and that the draft of the 

updated statement would be presented during this session: 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

 Review existing statements on infants and young children (1997), adolescent (2006), adults 

(2006), and pregnant and postpartum women and their infants (2008) and consolidate into a 

single statement 

 Review new data on Tdap including 

 Effectiveness of ACIP recommendations 

 Interval between Td booster and Tdap 

 Use of Tdap in adults ages 65 years and older 

 Pregnant and breastfeeding women 

• Use of Tdap 

• Cocooning strategies 

 Vaccinated HCP and need for post-exposure prophylaxis 

 Tdap revaccination 

• Pregnant women 

• Healthcare personnel 

• “Cocooning” 

 Review updated epidemiology of tetanus and diphtheria in the US 

As a reminder, there are two types of pertussis, tetanus, and diphtheria vaccines. The first is 

DTaP (diphtheria and tetanus toxoids and acellular pertussis), which is the pediatric vaccine. 

The second is Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), which is 

the same as DTaP but with reduced quantities. This is the adolescent and adult vaccine that is 

licensed for single use only. 

In the time since ACIP recommended Tdap for pregnant women, additional studies have 

assessed the safety and immunogenicity of Tdap vaccination during pregnancy, and the 

effectiveness of preventing infant pertussis. It was timely and critically important for the WG to 

review these data, given that the updated statement for pertussis, tetanus, and diphtheria 

vaccines was being prepared for ACIP’s review and affirmation. 

Tdap coverage among pregnant women has steadily increased. The current estimate during 

influenza season from an Internet Panel Survey is 48.8% [CDC. Internet Panel Survey. Women 

aged 18–49 years pregnant at any time since August of prior year (e.g. 2015 for the April 2016 

survey)]. 

With regard to the updated statement and the historical background of the ACIP statements, the 

first acellular DTaP vaccines were licensed by the Food and Drug Administration (FDA) and 

recommended by ACIP for the 4th and 5th dose in 1991. In 1997, ACIP recommended DTaP for 

all 5 doses in the childhood schedule. In 2005, Tdap was first licensed by the FDA and then 

recommended by ACIP for a single dose for adolescents and adults. Since the 2005 Tdap 

recommendations, ACIP has expanded and updated the Tdap recommendations, which were 

published as Policy Notes in the MMWR. In 2010, ACIP recommended that Tdap should be 

administered regardless of interval since last tetanus or diphtheria toxoid-containing vaccine. 

This included a permissive Tdap recommendation for adults aged 65 years or older, as well as a 

catch-up schedule for children aged 7 through 10 years to receive a single dose of Tdap1. In 

2011, ACIP recommended a dose of Tdap during pregnancy for women who previously have 

not received Tdap2. In 2012, ACIP routinely recommended a single dose of Tdap for adults 

aged 65 and older and a dose of Tdap during every pregnancy3,4 [

1CDC. MMWR 2011;60;13–5; 

2CDC. MMWR 2011;60:1424–6; 3CDC. MMWR 2012;61;468-470; and 4CDC. MMWR 

2013;62;131-135]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Vaccination rates among children are high. Unlike Tdap coverage among adults, adolescent 

Tdap immunization has increased steadily since its introduction: 

This session focused on the guidance for the use of Tdap in pregnant women; and the updated 

ACIP statement for pertussis, tetanus, and diphtheria for a vote. 

Guidance on Timing of Tdap Administration During Pregnancy 

Jennifer L. Liang, DVM, MPVM 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Before focusing on the topic of timing of Tdap administration during pregnancy, Dr. Liang 

indicated that because the pertussis WG had not presented to ACIP in over a year, she would 

give an overview of the epidemiology of pertussis in the US, the current ACIP Tdap 

recommendation and guidance for use for pregnant women, and the safety of Tdap 

administration to mothers and their infants. 

Following the introduction of whole-cell pertussis vaccines (DTP) in the late 1940s, there was a 

dramatic decline in cases reported through the NNDSS. In the 1990s, the US transitioned from 

whole-cell to acellular pertussis vaccine (DTaP). By 1997, all 5 doses of the childhood series 

were DTaP. Tdap vaccine was introduced in 2005. Since the late 1980s, the burden of disease 

has been increasing, with notable epidemic years in 2004, 2010, and most recently in 2012, with 

over 48,000 cases reported. The increases in reported pertussis cases over the last two 

decades are likely the result of a number of factors, including improved surveillance capacity; 

changes in diagnostic testing and reporting; increased public and provider awareness; and 

probably most importantly, waning protection from acellular pertussis vaccines. 

Historically, rates of pertussis have remained about the same for all age groups until more 

recent years when the emergence of disease has been observed in 7 to 10 year olds and 11 to 

19 year olds. A growing body of evidence, which has been presented to ACIP throughout the 

years, strongly suggests that the change in vaccines from whole-cell to acellular pertussis 

vaccines in the childhood vaccine series has caused the age-specific increases due to waning 

immunity. Infants continue to have the highest risk for disease [CDC, National Notifiable 

Diseases Surveillance System and Supplemental Pertussis Surveillance System]. 

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Published studies have found that acellular pertussis vaccines provide protection within the first 

year of receipt, but that effectiveness wanes over time. Vaccine effectiveness for DTaP was 

evaluated by time since the 5th DTaP dose1. Tdap vaccine effectiveness was evaluated in 

adolescents who received only acellular pertussis vaccines for the primary DTaP series2 

[

1Misegades LK, et al. JAMA. 2012 Nov 28;308(20):2126-32; 2Acosta AM, et al. Pediatrics. 

2015;135:981–9]. 

 

 

Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

As previously mentioned, infants continue to have the highest risk for disease. This graph 

shows the number of reported deaths by age group and year. Infants less than 3 months of age 

(in beige) account for the greatest number of reported deaths from pertussis: 

Of reported infant pertussis cases who were hospitalized, more that 50% were less than 2 

months of age. Of those who died, 86% were less than 2 months of age. These infants were 

too young to have received any doses of pertussis vaccines. Because young infants are 

vulnerable to pertussis infection and have the highest morbidity and mortality rates of pertussis, 

as a strategy to prevent infant pertussis, ACIP first recommended a single dose of Tdap for 

pregnant women in 2011. Prior to this recommendation, Tdap was recommended to be given to 

women postpartum. In 2012, ACIP expanded the recommendation to a dose of Tdap during 

every pregnancy. This is the ACIP Tdap recommendation for pregnant women and guidance 

for use: 

ACIP Tdap Recommendation for Pregnant Women 

 ACIP recommends that providers of prenatal care implement a Tdap immunization 

program for all pregnant women. Health-care personnel should administer a dose of 

Tdap during each pregnancy, irrespective of the patient’s prior history of receiving 

Tdap. 

Guidance for Use 

 To maximize the maternal antibody response and passive antibody transfer to the 

infant, optimal timing for Tdap administration is between 27 and 36 weeks gestation 

although Tdap may be given at any time during pregnancy. For women not 

previously vaccinated with Tdap, if Tdap is not administered during pregnancy, Tdap 

should be administered immediately postpartum. 

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The focus of the WG’s review and discussion is the language in the guidance for use that 

states, “To maximize the maternal antibody response and passive antibody transfer to the 

infant, optimal timing for Tdap administration is between 27 and 36 weeks gestation although 

Tdap may be given at any time during pregnancy.” 

As a reminder, 2 Tdap vaccines are available in the US: Sanofi Pasteur’s ADACELTM and 

GlaxoSmithKline’s (GSK’s) BOOSTRIX®. Both provide protection to pertussis, diphtheria, and 

tetanus. For pertussis antigens, both products contain pertussis toxin (PT), filamentous 

hemagglutinin (FHA), and pertactin (PRN). ADACELTM also contains fimbriae (FIM). 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

When ACIP first recommended Tdap to pregnant women, safety data, although reassuring, 

were limited. ACIP stated the need for enhanced monitoring and safety studies of Tdap given 

during pregnancy, especially to women who have received prior Tdap vaccination. In response 

to ACIP’s comments, the CDC Immunization Safety Office (ISO) developed an immunization 

safety plan for this population through 3 established post-licensure vaccine safety monitoring 

infrastructures: 

 Vaccine Adverse Event Reporting System (VAERS) 

 Vaccine Safety Datalink (VSD) 

 Clinical Immunization Safety Assessment (CISA) Project 

CDC monitoring activities for maternal Tdap safety include ongoing monitoring through VAERS 

and VSD. VSD provides available coverage data, as well as surveillance and research on 

safety signals including: preterm delivery and small for gestational age (SGA), acute vaccinerelated AEs, obstetric events, and birth defects. VSD also has access to electronic medical 

records (EMRs) and medical records to validate cases and denominators for rates. CISA 

currently has 2 projects: 1) Tdap safety in pregnant women; and 2) the safety of simultaneous 

Tdap Inactivated Influenza Vaccine (IIV) in pregnant women. Safety data from these monitoring 

activities have been presented to ACIP at past meetings. 

Safety data collected in the US on Tdap in pregnant women and infants continue to be 

reassuring. The pattern of AEs observed in VAERS in pregnant women receiving Tdap and 

their infants is consistent with expectations. Studies of over 50,000 women receiving Tdap 

during pregnancy in the VSD show no increased risk for adverse maternal or infant health 

outcomes. A clinical study in the CISA Project shows that Tdap was well-tolerated in both 

pregnant and non-pregnant women, including pregnant women receiving a repeated Tdap dose 

[Kharbanda EO et al. JAMA. 2014;312(18):1897-904.; Sukumaran L, et al. JAMA. 2015 

314(15):1581-7, Sukumaran L, et al. ObGyn. 2015;126(5): 1069–1074; Kharbanda EO et al. 

Vaccine 2016; 34: 968-73]. 

Although pertussis-specific antibodies likely would confer protection and modify the severity of 

pertussis illness, when ACIP first recommended Tdap for pregnant women, the effectiveness of 

Tdap vaccination during pregnancy to prevent infant pertussis was not known. Since then, 

effectiveness data and additional immunogenicity data have become available. Recent 

immunogenicity studies have assessed the optimal timing of Tdap administration during 

pregnancy to provide maximal transfer of maternal antibodies to infants. Before presenting a 

summary of these studies, Dr. Liang highlighted some additional information. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

For pertussis, there are no well-defined serologic correlates of protection. PT is suggested to 

be the most important virulence factor. After receipt of Tdap, a minimum of 2 weeks is needed 

to mount a maximal immune response to the vaccine antigens. During the course of pregnancy, 

active immunoglobulin G (IgG) transport begins around 17 weeks gestation and increases with 

gestational age, with accelerated uptake starting around 34 weeks. The immune response in 

pregnant women to Tdap immunization is similar to non-pregnant women, and vaccine-induced 

pertussis antibodies are efficiently transplacentally transferred from a woman to her fetus. 

Studies report higher antibody concentration in infant cord blood compared to maternal serum. 

An Australian study from Naidu et al examined and compared cord blood pertussis antibody 

levels for PT, FHA, and PRN in infants of unvaccinated and vaccinated mothers. Compared to 

the no Tdap group, cord blood antibody levels were significantly higher in the vaccinated 

groups. By multivariable analysis, when adjusted for maternal pre-vaccination levels, pertussis 

toxin approached significance and PRN was significantly higher in the early versus late 

vaccination group. Naidu et al also found a modest to significantly positive correlation between 

the number of weeks exposed to Tdap and infant cord blood levels for the three pertussis 

antibodies. These findings suggest that longer exposure to vaccine allows for higher vaccineinduced antibody levels produced by the mother and transferred to the infant, which supports 

earlier vaccination within the 27 through 36 week window [Naidu et al. Pertussis vaccination 

during pregnancy. Am J Obstet Gynecol 2016. (Australia)]. 

As with the previous study, a study from Abu Raya et al found both maternal and infant cord 

blood sera concentrations were higher in the Tdap vaccinated groups versus the unvaccinated 

group. Within the 27 through 36 week window of Tdap administration, the cord blood GMC for 

PT was higher in infants whose mothers received Tdap at 27 through 30 weeks compared to 31 

through 36 wks. It is unclear why the GMCs are higher for Tdap after 36 weeks, but this is from 

a smaller group and the findings are not consistent with other studies [Abu Raya et al. The 

effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization 

during pregnancy on newborn pertussis antibody levels – A prospective study. Vaccine 2014. 

(Israel)]. 

A study by Dr. Mary Healy from Baylor College of Medicine looked at anti-PT specific IgG levels 

in cord blood from infants born to women who received Tdap during weeks 27 through 36 

weeks gestation compared with infants of unvaccinated mothers. As part of this study, Dr. 

Healy assessed the optimal gestation for Tdap administration between 27 through 36 weeks. 

This study shows that immunization earlier within the 27 through 36 weeks appears to allow for 

maximal anti-PT IgG antibodies in infants [Unpublished data courtesy of CM Healy, Baylor 

College of Medicine]. 

The aim of a Swiss study by Eberhardt et al was to determine whether Tdap vaccination as 

early as 13 through 25 weeks would elicit non-inferior geometric mean concentrations (GMCs) 

of infant cord blood antibodies compared with immunization after 25 weeks gestation. Within 

the current ACIP guidance, infant cord blood GMCs for PT and FHA tended to be higher for 

infants whose mothers received Tdap between 26 through 33 weeks compared to infants whose 

mothers received Tdap after 33 weeks gestation. Eberhardt also found that the GMCs were 

non-inferior for infants whose mothers received Tdap earlier than 26 weeks [Eberhardt et al. 

Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant 

Seropositivity Against Pertussis. CID 2016. (Switzerland)]. 

From the Eberhardt et al study, these curves represent the distribution of individual anti-PT 

antibody GMCs at various time intervals between maternal Tdap immunization and delivery: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

There is a red box around the days that would fall within the 27 through 36 week window. 

Compared to no vaccination and less than 15 days before delivery (pink and blue lines), a 

longer time between maternal Tdap and before delivery resulted in similar distribution of anti-PT 

infant cord blood concentrations. Antibody concentrations markedly increased with intervals 

greater than 14 days, reaching optimal GMC with intervals between 31 and 120 days. 

In summary of the immunogenicity studies, infants of mothers vaccinated with Tdap during 

pregnancy were born with significantly higher anti-pertussis antibodies compared to infants of 

unvaccinated mothers. Within the 27 though 36 week window, the concentration of antipertussis antibodies in infant cord blood were generally higher when mothers were vaccinated 

earlier. In addition, longer exposure to vaccine allows for higher vaccine induced antibody 

levels produced by mother and transferred to infant. One study found infant cord blood 

concentration of anti-pertussis antibodies non-inferior when maternal Tdap was administered 

before 27 weeks. 

Although the methodologies differ, several studies have shown that vaccinating women during 

pregnancy is very effective at preventing infant pertussis, from 78% to 93% effective. The 

majority of women from these studies were vaccinated within the current guidance window of 27 

through 36 weeks: 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

A retrospective cohort study from California evaluated whether infants born to mothers who 

received Tdap during pregnancy had less severe pertussis compared to infants born to 

unvaccinated mothers. Infected infants of vaccinated mothers were older when they developed 

disease and were less likely to have classic pertussis symptoms. They also were at significantly 

lower risk of hospitalization and intensive care unit (ICU) admission. None of these infants 

developed seizures, required intubation, or died [Winter K, et al. Effectiveness of prenatal Tdap 

vaccination on pertussis severity in infants. Clin Infect Dis. 2016 Sep 13. (Epub ahead of print)]. 

After review of available data on immunogenicity and effectiveness, the WG was cautious with 

how these immunogenicity data might relate to effectiveness. Again, the minimal concentration 

of antibodies to confer protection is unknown. Because of this unknown, the WG noted that it is 

important to ensure enough time between mother’s receipt of Tdap and infant’s birth to allow for 

maximizing the concentration of maternal antibodies. This may be better achieved by 

vaccinating at an earlier gestational age (e.g., before 27 weeks gestation). However, 

vaccination too early during pregnancy may not allow for sustained levels of antibodies to 

provide protection through the infant’s first DTaP dose at age 2 months due to maternal 

antibody decay. Data are not yet available to address this concern. 

Based on review of the immunogenicity and effectiveness data, the WG considered the 

following options to modifying the current window: 

1.	 Expanding the window to include earlier Tdap administration (e.g., as early as 22 weeks) 

2.	 Narrowing the window to 27 through 32 weeks 

3.	 No change to the current window of 27 through 36 weeks, but emphasize earlier 

administration within the window 

When reviewing these 3 options, the WG considered what the impact any modification to the 

guidance window would have on the current program. ACIP has been recommending Tdap for 

pregnant women since 2011. Since then, Tdap uptake in pregnant women has steadily 

increased. As Dr. Riley presented earlier, the current estimate from the 2015-2016 influenza 

Internet Panel Survey was 48%. During the previous flu season, Tdap coverage was 23%. The 

WG did not want to potentially disrupt this trend. Earlier administration of Tdap might increase 

the opportunity to educate and vaccinate pregnant women and increase protection among 

preterm infants. Vaccinating pregnant women earlier might provide protection to the earliest 

preterm infants, but the great majority of preterm infants are provided protection under the 

current 27 through 36 week window. When considering narrowing the window, the WG was 

concerned this would decrease the opportunity to vaccinate pregnant women. 

The WG is encouraged that vaccinating pregnant women with Tdap is effective at preventing 

pertussis in infants. The WG also was reassured that if infected with pertussis, infants born to 

vaccinated mothers are less likely to develop severe pertussis compared to infants born to 

unvaccinated mothers. Although there is variation between immunogenicity studies, and the 

studies are limited by small to modest samples sizes, these studies have shown that vaccinating 

earlier within the 27 through 36 week window or even before 27 weeks may be beneficial in 

optimizing the production and transfer of maternal antibodies to infants. However, it is unclear 

at this time how the immunogenicity data from earlier administration will translate to 

effectiveness in preventing infant pertussis. The current strategy is effective at preventing infant 

pertussis, so the WG was reluctant to modify the current window. Again, the WG was cautious 

not to equate higher concentration of maternal antibodies from earlier vaccination to similar or 

better effectiveness without knowing whether the durability and concentration of maternal 

antibodies would be maintained until an infant is old enough to receive his or her first DTaP. 

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Without effectiveness data specific to vaccinating women earlier during pregnancy, the WG is 

cautious to over-interpret results from these studies. 

After considering the proposed options, the WG did not support expanding the window to 

include earlier Tdap administration. Although the WG thought that vaccinating earlier within the 

current window likely would provide maternal antibodies for the majority of infants including 

those born preterm, WG members differed in how to modify the current guidance of 27 through 

36 weeks. A minority of the WG supported narrowing the current window to 27 through 32 

weeks; whereas, a majority supported no change to the current window of 27 through 36 weeks, 

but including language to emphasize earlier administration within this window. This option also 

was supported by the American Congress of Obstetricians and Gynecologists (ACOG) and the 

American College of Nurse Midwives (ACNM) WGs. Therefore, the language Dr. Liang 

presented was modified accordingly. 

As a reminder, here is the current ACIP Tdap recommendation for pregnant women along with 

the guidance for use. The underlined sentence in the Guidance for Use is the language the WG 

is updating: 

ACIP Tdap Recommendation for Pregnant Women 

 ACIP recommends that providers of prenatal care implement a Tdap immunization 

program for all pregnant women. Health-care personnel should administer a dose of 

Tdap during each pregnancy, irrespective of the patient’s prior history of receiving 

Tdap. 

Guidance for Use (CURRENT) 

 To maximize the maternal antibody response and passive antibody transfer to the 

infant, optimal timing for Tdap administration is between 27 and 36 weeks gestation 

although Tdap may be given at any time during pregnancy. For women not 

previously vaccinated with Tdap, if Tdap is not administered during pregnancy, Tdap 

should be administered immediately postpartum. 

The drafted change to the Guidance for Use is shown below. The underlined sentence is the 

WG’s proposed updated language: 

Guidance for Use (DRAFTED CHANGE) 

 Tdap should be administered between 27 and 36 weeks gestation, although it may be 

given at any time during pregnancy. Currently available data suggest that vaccinating 

earlier in the 27 through 36 week window will maximize passive antibody transfer to the 

infant. For women not previously vaccinated with Tdap, if it is not administered during 

pregnancy, Tdap should be administered immediately postpartum. 

This guidance language will be included in the updated ACIP statement for pertussis, tetanus, 

and diphtheria vaccines, which Dr. Liang presented following this discussion. 

Discussion Points 

Acknowledging that there are not specific data about duration of maternal antibody if given 

earlier, Dr. Kempe said she would not expect this to be very different from other situations. She 

asked Dr. Liang to talk about what the subject matter experts (SMEs) thought about duration 

(e.g., the comparison between 22 weeks or 27 weeks). 

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Dr. Liang replied that while the immunogenicity showing equivalent or non-inferior concentration 

to earlier administration were promising, the WG was concerned that without knowing the 

durability and timing of maternal antibody decay, whether that higher concentration would 

translate to durability from time of birth to 2 months of age when the infant would be 

recommended to receive the first dose of DTaP. 

Dr. Walter asked whether that was the WG’s main consideration in not narrowing the window to 

an earlier time. 

Dr. Liang responded that that was one of the considerations. The other concerns regarded 

potential programmatic disruption. Any change potentially could cause confusion. They have 

heard anecdotally that even with the current guidance window, providers are not necessarily 

targeting between the 27 through 36 weeks. Any other change potentially would result in 

misinterpretation. Because the data are not available at this time, the WG did not want to 

change the recommendation drastically. 

Dr. Riley added that the concern was that it would be making another small change in the 

context of only 48% uptake with a fairly new recommendation, which could cause more 

confusion. It has been observed that when people do not understand a change, they tend to do 

nothing. The goal is to get people vaccinated. Even if women are vaccinated at 36 weeks, it is 

better than not getting vaccinated at all. Because of the goal to shift vaccination to the earlier 

end of the range, ACOG intends to tell obstetricians that if this is paired with the glucose test 

that everyone has at approximately 27 to 28 weeks, this would be an ideal time to give Tdap as 

well. The hope is that people will vaccinate earlier in the window. The other concern is that 

when vaccination is given at 34 and 36 weeks, it misses all of the late pre-term infants who get 

nothing. 

Dr. Liang said that given the various studies that have evaluated the effectiveness in preventing 

pertussis in infants, and because those evaluations were done within the current window of 

administration, the WG felt that was reassuring and showed that the current program is working. 

Whether to shift it to make it earlier, they didn’t have these data. Within the US, the 

evaluations—the coverage, they are still learning about impact. They know that it works in the 

individual infant, but in terms of overall numbers of cases reported in infants, we’re just starting 

to be able to evaluate that as coverage increases and moving forward through time. 

Dr. Szilagyi asked whether there are any healthcare utilization data that would suggest what 

percentage of pregnant women would not be seen at all if the window were narrowed, resulting 

in a missed opportunity to vaccinate them. 

Dr. Liang replied that they do not have these data. While it is known that there are providers 

who are administering Tdap, it is not known when specifically they are administering it even 

during pregnancy. There is a lot of variability. One of the limitations of the coverage data is that 

while it is known that pregnant women are receiving Tdap, when they receive it during 

pregnancy is unknown. 

Dr. Hunter asked whether it would be possible to acquire data about frequency by week of 

pregnancy. He noticed on one of slides that there were data about that in a small group. It 

looked like it was between 27 and 30 weeks, and then dropped off after that. He assumed that 

had to do with the protocols of when it is given, and group-by-group how practices decide to set 

things up in their clinics. 

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Dr. Riley responded that it probably reflects how people are implementing the protocol. The 

thought is that if the ACOG statement stresses that earlier in the existing window is better for X, 

X, and X reasons and it is paired with the glucose test, more women will receive the vaccine at 

27 to 28 weeks. The WG discussed making it 26 weeks. The concern is that little changes 

make people do odd things. 

Dr. Messonnier emphasized that studying this is very difficult and there is a lot of variability in 

the datasets about when people get vaccinated. While there are data on the overall vaccine 

efficacy of the program, there are no data that take timing into account. It also is important to 

remember that there are two vaccines, and there are some data to suggest that the kinetics of 

the vaccines differ. The UK will be changing their window, so this is a case in which additional 

data will be available in a couple of years from a setting of high vaccination coverage. 

Dr. Stanley Plotkin (Audience Member) said he thought the recommendation to maintain 27 to 

36 weeks was a reasonable public health recommendation. However, he objected to the 

mantra that the correlates of protection are unknown. Obviously, this is known. The fact that 

maternal immunization protects infants shows that, in fact, antibody is the correlate of 

protection. What is not known is an absolute threshold for the antibody. But it is very clear that 

antibodies to PT, FIM, and PRN are protective. Personally, he believes that vaccinating early in 

the third trimester is better than vaccinating later because of the antibody data. He thinks it is a 

reasonable compromise under the current circumstances to maintain the breadth of the 

recommendation, particularly since the impact on later vaccination of the infant has to be taken 

into account in making the overall recommendation. 

Having reviewed the data as the WG has, Dr. Neuzil (IDSA) also believes that it appears that 

earlier is better though how early is not quite clear. However, she was not certain that the 

statement reflected the WG’s intent and that it may not be strong enough. While she 

appreciated the issue of not wanting to tweak, she asked whether consideration was given to 

recommending that the vaccine should be administered during the first visit of the third 

trimester, or as early as possible in the third trimesters, and then putting that 27 through 36 in 

parentheses. As Dr. Riley said, it is very protocol-driven in obstetrics. If they could get it right 

there with the first third trimester visit, that might accomplish this without causing confusion. 

Dr. Belongia supported that. He suggested that the second sentence would be stronger if it 

read, “Vaccine should be administered as early as possible within the 27 through 36 week 

window.” 

Dr. Hayes (ACNM) emphasized that the WG felt that they should be careful about 

recommendation fatigue, which was one of the primary reasons that this was not changed. In 

regard to the question about data and utilization, ACNM has a Maternal Immunization Working 

Group that is trying very hard to get a quality data measurement on this. They were not happy 

because they have been working for a year and a half on this language, which is what they 

planned to measure. She issued a plea on behalf of the ACNM Maternal Immunization Working 

Group not to change the language. She did agree that the language could be stronger. 

Dr. Riley said she was perfectly fine with saying “earlier within the window.” She cautioned 

against saying “the first visit in the third trimester” because that definition is a moving target. 

Some people say the third trimester is 24 weeks, some say 26, and others say 28. If the 

recommendation is too literal, someone at 25 weeks might not get the vaccine. 

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Dr. Bennett noted that the plan was to vote on the updated statement, not this particular 

wording. 

Dr. Friedland (GSK) mentioned that in addition to the safety programs outlined by Dr. Liang, 

GSK maintains a pregnancy registry for the use of BOOSTRIX® in the US and in other parts of 

the world. They have ongoing pharmacovigilance systems in place to monitor the safety of the 

use of BOOSTRIX® in pregnant women around the world. 

Dr. O’Leary (PIDS) thought that “earlier in the window” was vague. He asked whether there 

was discussion about being more specific, such as stating 27 to 30 weeks, or 27 to 29 weeks, 

just thinking about the protocolization. 

Dr. Riley stressed that from a programmatic standpoint, if it is timed with the glucose loading 

test that obstetricians do at a certain time all of the time, this probably would be earlier in the 

window. 

An inquiry was posed regarding what the wording is on the glucose testing, and whether it is 

tied to a trimester. 

Dr. Riley replied that it is generally given at 26 to 28 weeks gestation. 

Dr. Wexler (IAC) said that they do receive a lot of questions about the last statement, “For 

women not previously vaccinated with Tdap, if it is not administered during pregnancy, Tdap 

should be administered immediately postpartum.” Providers want to know, even if women were 

vaccinated at 11 or 12 years of age, why not protect them immediately with a dose of Tdap. 

Dr. Belongia asked what is known about co-administration of influenza vaccine and Tdap in 

pregnancy, and whether there is a specific recommendation and if there is any evidence that 

receipt of one might influence the immunologic response to the other. 

Dr. Liang replied that at this time, a CISA study is just beginning to assess this. Currently, there 

is no language that states not to co-administer Tdap with influenza vaccine. One study has 

evaluated co-administration of these two vaccines in non-pregnant populations, which found 

that there was a slight decrease in the response in one of the pertussis antigens. However, it is 

not known what that translates to in terms of clinical outcome or the impact of the response. 

Updated ACIP Statement for Pertussis, Tetanus, and Diphtheria Vaccines 

Jennifer L. Liang, DVM, MPVM 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Liang explained that the updated statement compiles and summarizes all previously 

published recommendations from CDC’s ACIP regarding prevention and control of pertussis, 

tetanus, and diphtheria in the US, specifically after the introduction of acellular pertussis 

vaccines, and does not contain any new recommendations. This document also provides an 

overview of the current epidemiology of tetanus, diphtheria, and pertussis; and an updated list of 

current vaccines and recommendations for routine vaccination and guidance for use. The 

statement also describes the process undertaken and the rationale used in support of these 

recommendations, and is intended for use by clinicians and public health providers as a 

resource. This statement is the product of the review of published DTaP and Tdap vaccine 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

recommendations, peer-reviewed literature, and surveillance data from NNDSS and Enhanced 

Pertussis Surveillance (EPS). The WG reviewed the draft statement and provided comments. 

Prior to this meeting, ACIP voting members reviewed the draft statement and provided 

comments. 

To summarize the updated statement, after the introduction of universal immunization with 

tetanus toxoid-containing vaccines in the mid-1940s, the incidence of reported tetanus in the US 

declined by more than 98%. Deaths from tetanus also declined similarly during this period. 

Currently, tetanus is rare in the US and occurs primarily among older adults. From 2005-2015, 

an average of 28 tetanus cases per year are reported. 

In the US, reported diphtheria cases from all anatomical sites declined from over 200,000 in 

1921 to 15,536 in 1940. This decline continued after the introduction of universal childhood 

immunization in the late 1940s. In 1980, only two cases of diphtheria were reported. During 

1996–2004, 11 cases were reported. From 2004-2011 no cases were reported, but in 2012, 

there was a probable case of nontoxigenic diphtheria, and in 2014 a confirmed case positive by 

culture with non-toxigenic C. diphtheriae. As previously presented, the following graph shows 

the number of reported pertussis cases in the US from 1922-2015: 

Listed here are the currently licensed and available DTaP vaccines, combination vaccines with 

DTaP, and DT vaccines in the US: 

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Following is a list of the currently licensed and available Tdap and Td vaccines in the US: 

Note that monovalent tetanus toxoid vaccine manufacturing was discontinued and has not been 

available in the US since 2013. 

The consolidated updated statement will contain the routine recommendations for DTaP, DT 

when indicated, Tdap, and Td which were last published in separate statements. The statement 

also includes Tdap recommendations made after the 2005 recommendations and published in 

MMWR Policy Notes. Again, there are no changes to these previously published 

recommendations. The statement also contains updates such as DTaP vaccines that became 

available after the 1997 DTaP statement, and updates to label indications for various DTaP and 

Tdap products. Also included in the statement are the following updates: 

 Mention of the discontinuation of monovalent tetanus toxoid (TT) vaccine 

 Contraindications and precautions for DTaP are now consistent with AAP’s Red Book 

 For persons aged 7 through 10 years who receive a dose of Tdap as part of the catch-up 

series, an adolescent Tdap vaccine dose may be given at age 11 through 12 years; this 

guidance is now in line with guidance given on children for which Tdap is inadvertently 

administered 

Dr. Liang explained that the ACIP vote for this session would be to affirm the updated 

statement, which does not contain any new vaccine recommendations. The statement will be 

updated with the modified Guidance for Use language of Tdap for pregnant women, along with 

a summary of supporting data. A table summarizing safety studies on use of Tdap in pregnant 

woman and their infants also will be included. Before the vote, Dr. Liang recognized and 

acknowledged all of the WG members from past and present who have been part of this 

process since 2009. She also thanked the previous WG chair, Dr. Mark Sawyer and current 

WG chair Dr. Art Reingold for their leadership. In addition, she acknowledged several CDC 

groups and CDC contributors on the WG for providing subject matter expertise. 

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Discussion Points 

Given that the guidance is part of the recommendations, Dr. Kempe asked for clarity regarding 

whether they were in fact voting on the language of the guidance as well. 

Dr. Cohn indicated that they were separating out recommendations from Guidance for Use. 

The Guidance for Use are CDC recommendations about how to implement the 

recommendations the ACIP votes on. It sounded like the WG could incorporate some of the 

discussion from earlier to modify that language. 

Ms. Stinchfield (NAPNAP) noted that a very common situation that she did not hear discussed 

regarded how to handle an adolescent who has not had a primary DTaP series, who presents to 

catch-up. 

Dr. Liang replied that there is catch-up language for a child, adolescent, or adult who presents 

wanting to receive any pertussis-containing vaccines that the catch-up series includes one dose 

of Tdap. 

Public Comment 

Christina Hildebrand 

A Voice For Choice Advocacy 

I was very interested in what you presented today, and I thank you for allowing me to give you 

public comment. I have some questions which seem to be left unanswered by the presentation. 

You said that you’re going to give a summary of Tdap safety studies. The vaccine package 

inserts for both Tdap studies state that there will be no clinical trial or studies on pregnant 

women for both of those studies, so I’m curious to get those Tdap safety studies that you 

mentioned. The studies that were outlined in the presentation have extremely small sample 

sizes, so I would hope that the studies that you are referring to have larger sample sizes. I also 

wonder whether there has been review of the number of miscarriages. The studies that I’ve 

seen actually took out stillborn deaths, and I wonder if we have any studies on the number of 

stillborn deaths and miscarriages that happen after vaccination versus those people who are not 

vaccinated. The other piece that I would ask that you address is that both Tdap vaccines 

include aluminum—we know aluminum crosses the blood-brain barrier (BBB)—and whether that 

has been studied in fetuses and whether the aluminum from the Tdap vaccine dose, in fact, 

crosses the BBB and what that does to the fetus. And then the other question that I have for 

you is that there have been studies in baboons that have shown that the DTaP and Tdap 

vaccines actually show that you can be an asymptomatic carrier of pertussis and you can 

actually give pertussis to someone else. And so, I wonder whether that has been addressed 

and whether the giving of Tdap and DTaP among infants, specifically Tdap among the parent, 

whether they can be an asymptomatic carrier to their infant, as well as whether giving the Tdap 

actually stops the infant from getting pertussis—whether in that first 6 months of life, whether 

those infants that have had higher antibodies have actually been stopped from getting pertussis. 

Also, because we know right now, most people and—most adults and most teenagers that are 

getting pertussis are getting it having been fully vaccinated. Thank you. 

Dr. Meissonier thanked Ms. Hildebrand for her questions and comments. She said she thought 

that one issue was that a lot of the information she was asking about was presented during a 

previous ACIP meeting. All of the ACIP members have seen those data and have had 

deliberations on it. That information is available online. In addition, she said that CDC’s SMEs 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

would be happy to speak with Ms. Hildebrand during the break and share data. The 

pharmaceutical companies also collect data pertaining to some of Ms. Hildebrand’s points. If 

the information is not clear in the package insert, she was sure the manufacturers would be 

happy to provide more information about that as well. 

James Grundvig 

Freelance Journalist, New York City 

Epoch Times, Financial Times, Foreign Direct Investment (FDI) Magazine 

My green investors would like to know why Zika wasn’t discussed with this particular vaccine. 

Apparently the microcephaly problems in Northeast Brazil has not been confirmed yet whether 

it’s Zika, whether it’s other toxins, or whether the vaccine was given down there to pregnant 

women. 

Dr. Bennett thanked Mr. Grundvig for his comment. She explained that ACIP focuses its 

attention on vaccine recommendations in the US, and that there would be an update on Zika 

during the second day of the ACIP meeting. 

Vote: Updated Statement for Pertussis, Tetanus, and Diphtheria Vaccines 

Dr. Walter motioned to approve the updated statement for pertussis, tetanus, and diphtheria 

vaccines. Dr. Riley seconded the motion. The motion carried unanimously with 14 affirmative 

votes, 0 negative vote, and 0 abstentions. The disposition of the vote was as follows: 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

Human Papillomavirus (HPV) Vaccines 

Introduction 

Allison Kempe, MD, MPH 

Chair, ACIP HPV Vaccines WG 

Dr. Kempe reminded everyone that since 2006, HPV vaccination has been recommended as a 

3-dose series. The ACIP HPV Vaccines WG and ACIP have reviewed data on 2-dose 

schedules over the last year, and a vote is scheduled for this meeting. 

During the February 2016 meeting, there were presentations and deliberations on the 

background on 2-dose schedules, 9vHPV 2-dose immunogenicity trial data, and 2-dose data for 

the 2vHPV and 4vHPV. 

During the June 2016 meeting, there were presentations and deliberations on HPV vaccine 

supply, duration of protection after a 3-dose series of 2vHPV and 4vHPV vaccination; impact 

and cost-effectiveness modeling for 2-dose schedules; review of post-licensure vaccine 

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effectiveness studies of 2vHPV and 4vHPV; Grading of Recommendation Assessment, 

Development and Evaluation (GRADE) for 2-dose schedules; and initial considerations for 

recommendations. 

Since June 2016, the WG has held monthly conference calls to review further data from the 

9vHPV 2-dose trial, including follow-up data through month 12 and data on intervals between 

doses; discussed policy options; and drafted recommendations. 

The FDA approved a 2-dose series for persons age 9 through 14 years on October 7, 2016. 

The updated 9vHPV label includes immunogenicity data from the trial and an updated Dosage 

and Administration section shown below: 

http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf 

Potential future issues for the HPV Vaccines WG are to: 1) revisit the wording for the routine 

recommended age groups; and 2) revisit the upper age recommendation for males, as some 

WG members and liaison members feel strongly about this. The WG felt that these issues would 

require more data and more discussion; therefore, it was decided that these topics be tabled for 

future meetings. 

Review of Evidence for a 2-Dose Vaccination Schedule 

Lauri Markowitz, MD 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

In this presentation, Dr. Markowitz provided an overview of evidence for 2-dose schedules. She 

started with some background information on HPV vaccines and recommendations, and then 

provided a summary of evidence of data presented to ACIP over the last two meetings on 2­

dose schedules, as well as some new data from the 9vHPV vaccine 2-dose trial. She ended 

with data on vaccine coverage in the US and programmatic considerations. 

By way of review, there are 3 HPV vaccines licensed in the US: bivalent (2vHPV), quadrivalent 

(4vHPV), and 9-valent (9vHPV). These are all virus-like particle (VLP) vaccines composed of 

the L1 major capsid protein. The 2vHPV is produced by GSK and 4vHPV and 9vHPV are 

produced by Merck. While all are VLP vaccines, they differ in the types they target, their 

production systems, and adjuvants. The first vaccine licensed was 4vHPV in 2006, and the 

most recent was 9vHPV in 2014. 

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In terms of changes in the recommendations since the beginning of the program, in 2006, 

4vHPV was licensed and recommended for routine vaccination of females. In 2009, 2vHPV 

was recommended as one of the vaccines that could be used for females. Also in that year, the 

4vHPV was licensed for use in males and ACIP made a statement that the vaccine may be 

given to males. In 2011, 4vHPV was recommended for routine vaccination of males. In 2015, 

after licensure of 9vHPV, that vaccine was recommended as one of 3 vaccines that could be 

used for females and one of 2 for males. Since the beginning of the program, a 3-dose series 

has been recommended. 

ACIP currently recommends routine vaccination at age 11 or 12 years. The vaccination series 

can be started beginning at age 9 years. Vaccination is recommended through age 26 for 

females and through age 21 for males not vaccinated previously. A 3-dose series is 

recommended at an interval of 0, 1-2 months, and 6 months. Since 2015, any of the three 

vaccines are recommended for females and 4vHPV or 9vHPV for males [MMWR 2015;64:300­

4]. 

Vaccine use and availability in the US is changing. Through 2014, almost all HPV vaccine used 

was 4vHPV. In 2016, almost all HPV vaccine used is 9vHPV (>90%). GSK made the decision 

to stop supplying 2vHPV in US due to low demand. In the US, 2vHPV supplies are expected to 

be used up by November 2016. Only 9vHPV has been on the CDC contracts since April 2016. 

Merck will distribute only 9vHPV in the US after October. 2vHPV and 4vHPV will continue to be 

available outside the US. 

In terms of the evidence considered by ACIP for the 2-dose recommendation over the past two 

meetings, for initial licensure of the HPV vaccines as a 3-dose schedule, efficacy and 

immunogenicity data were obtained. These included efficacy data from large randomized 

controlled trials (RCT) trials in 15 through 26 year olds, with trial endpoints of cervical precancer lesions and well as some other pre-cancers and genital warts for 4vHPV v [Future II 

Study Group, NEJM 2007; Garland NEJM 2007; Paavonen Lancet 2007], and data from 

bridging immunogenicity trials in 9 through 15 year olds. Licensure in 9 through 15 year olds 

was based on non-inferior antibody response compared with young adult women in the efficacy 

trials. 

The 3-dose schedule for which vaccines were originally tested and licensed at a 0, 1 to 2, and 6 

months schedule can be considered a prime-prime-boost, with the first 2 doses being the 

priming doses and the third being the boost. The 2-dose schedules that are being studied, such 

as the 0, 6 months schedule, can be considered a prime boost with the second prime being 

eliminated. Memory B cells require at least 4 to 6 months to mature and differentiate into highaffinity B cells. The approximate 6-month interval between the first and last dose allows the last 

dose to reactivate memory B cells efficiently. 

The evidence reviewed for 2-dose schedules by the WG and ACIP include data on 

immunogenicity, post-hoc analyses of efficacy data, and post-licensure effectiveness data, and 

data from modeling and duration of protection. Dr. Markowitz reviewed each of these briefly. 

Most of the data used for evidence on 2-dose schedules are immunogenicity data. 

Immunogenicity trials comparing 2 and 3 doses have been conducted for all three HPV 

vaccines. The main analyses, and those considered by regulatory agencies, are comparisons 

of the antibody response after 2 doses in young adolescents about 9 through 14 years of age, 

with 3 doses in young adult women about 16 through 26 years of age. Again, the comparison 

group in these immunobridging analyses is the age group and the vaccine schedule for which 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

efficacy demonstrated in large RCTs. Immunobridging analyses are used because although the 

basis of protection after vaccination is thought to be due to the neutralizing antibody after 

vaccination, there is no established minimum threshold for protection. Trials of all three HPV 

vaccines found the antibody response after 2 doses given at a 0, 6 or 0, 12 month interval in 

those approximately 9 through 14 years of age to be non-inferior to the antibody response after 

3 doses in the older age group. Some trials also compared 2 and 3 doses in those 

approximately 9 through 14 years of age, with the results varying by trial. Antibody titers were 

lower after 2 doses versus 3 dose for some the HPV types in some of the trials. Based on data 

from immunogenicity trials, regulatory authorities have approved 2-dose vaccination schedules 

for HPV vaccines. These schedules are being used in multiple countries worldwide. 

With regard to the study design of the 9vHPV trial which led to FDA approval of a 2-dose 

schedule, there were 5 study arms. Three arms were among 9 through 14 year olds: 1) girls 

who received vaccine at a 0, 6 months interval; 2) boys who received vaccine at a 0, 6 months 

interval, and 3) a combined group of girls and boys who received vaccine at 0, 12 months 

interval. Two groups received a 3-dose schedule: 1) females 16 through 26 years of age, who 

were defined as the control group, and 2) females 9 through 14 years of age, who were used for 

an exploratory comparison. The primary analyses were at 1 month post-last dose. These were 

the data reviewed by the FDA and results were presented to CDC and ACIP in February 2016. 

Follow-up to assess antibody persistence is planned at months 12, 24, and 36. 

At one month after the last dose, there were non-inferior geometric mean titers (GMTs) in girls 

who received 2 doses at 0,6 months compared with women who received 3 doses at 0,2,6 

months. The GMTs were, in fact, higher at the younger age. The GMT ratios range from 1.60 

to 2.96 for the different types, with lower bound of the confidence interval (CI) above 1 for all 

types. The results for the comparison with the boys who received vaccine at 0, 6 months were 

similar. There were similar findings in the 2-dose 0,12 month group with non-inferior GMTs at 

one month post-last dose in girls and boys who received 2 doses at 0,12 months compared with 

women who received 3 doses at 0,2,6 months. Again, the GMTs were not only non-inferior, but 

also were higher in the younger age group that received 2 doses. The GMT ratios for each of 

the 9 types ranged from 1.96 to 6.31 [http://www.fda.gov/downloads/ 

BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf]. 

At the time of the presentation to ACIP in February 2016, only the data from 1 month after the 

last dose were available. Recently, the WG reviewed data from 6 months after the last dose. 

Data from 6 months after the last dose are not yet available for the 2-dose 0, 12 month group. 

Just looking at HPV6 as an example, GMTs decreased in all groups between these two time 

points, consistent with what has been seen for other HPV vaccination follow-up studies. At 

month 12, which is 6 months after the last dose, GMTs in both of the 2-dose groups were noninferior and higher than those in women who received 3 doses. The GMT ratios for girls 

compared with women was 2.15 at month 7 and 1.69 at month 12. There were similar findings 

for HPV 11 and 16. In terms of the other types targeted by the 9vHPV at 1 and 6 months after 

the last dose (months 7 and 12), for types 18, 31, and 33, GMTs were higher in the 2-dose 

groups compared with women who received 3 doses at both time points. For types 45, 52, and 

58 comparing the 2-dose 9 through 14 year olds and the 3-dose 16 through 26 year olds, GMTs 

decreased between 1 month and 6 months after the last dose. This is not unexpected and also 

was seen in the 4vHPV 2-dose trial in which GMT ratios also decreased initially, but stabilized 

between months 24 and 36. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Additional data reviewed by the WG from the 9vHPV 2-dose trial included data on GMTs by the 

interval between dose 1 and dose 2 in the 2-dose groups. This was to inform decisions about 

minimum intervals. In the 2-dose trial, the interval between 2 doses in the 0, 6 month group was 

6 months plus or minus 4 weeks. Over half of the vaccinees received dose 2 between 5 and 

less than 6 months after dose 1. This table shows GMTs for 4 of the types by interval between 

dose 1 and dose 2 in the 0, 6 month 2-dose group: 

Assay (cLIA) 

(0, 6) Girls (0, 2, 6) Women 

5 months to 

<6 months 

(N=162) 

≥6 months to 

7 months 

(N=112) 

5 months to 

7 months 

(N=286) 

Anti-HPV 6 1613 1720 771 

Anti-HPV 11 1333 1468 581 

Anti-HPV 16 7845 8238 3154 

Anti-HPV 18 1821 1949 762 

N=number of subjects in the per-protocol population for ≥1 HPV type 

cLIA = Competitive Luminex immunoassay 

GMTs expressed in milli-Merck units per milliliters (mMU/mL) 

GMTs were similar if dose 2 was administered at 5 to less than 6 months or ≥6 months to 7 

months after dose 1. For both intervals and all HPV types, GMTs were numerically higher than 

in women who received 3 doses, shown in the last column above. The updated 9vHPV label 

indicates a 2-dose series at 0 and 6-12 months and also states a minimum interval between 

dose 1 and dose 2 of 5 months. 

In summary, in the 9vHPV immunogenicity trials, immunogenicity is 97.8% to 100% seropositive 

to all 9 types 1 month after last dose. Compared with 3 doses in 16 through 26 year olds, 

antibody titers were non-inferior and significantly higher 1 month after the last dose. After2­

doses (0, 6 months or 0, 12 months) in the 9 through 14 year olds GMTs remained non-inferior 

and higher 6 months after the last dose. GMTs by interval between 2 doses in the 2-dose 0, 6 

month group support a minimum interval of 5 months between the two doses. Follow-up of the 

9vHPV 2-dose trial will continue through 36 months. As Dr. Kempe showed earlier, the FDA 

approved a 2-dose schedule for persons age 9 through 14 years on October 7, 2016. The label 

includes data from the 2-dose trial, as well as an updated Dosage and Administration section 

that states a 0, 6-12 month regimen and the minimum interval between doses. 

ACIP also reviewed immunogenicity data on 2-dose vaccination schedules for 2vHPV and 

4vHPV. As just discussed, in all trials, 2 doses at 0, 6 or 0, 12 months in those 9 through 14 

years of age were non-inferior to 3 doses in older age group. These trials provide important 

information because there is longer follow-up than in the trial of the 9vHPV vaccine. While there 

are differences in the vaccines, these studies do provide relevant data on persistence of 

antibody after vaccination. The longest follow-up for the 2vHPV is 60 months, for 4vHPV is 36 

months, and for 9vHPV vaccine is 12 months [Romanowski, Hum Vaccin Immunother 2016; 

Puthanakit, JID 2016; Lazcano-Ponce, Vaccine 2014; Dobson, JAMA 2013; Hernández-Ávila, 

Hum Vaccin Immunother 2016]. Another reason that these data were reviewed is that although 

4vHPV will not be marketed in the US after October, many individuals have received 4vHPV in 

the US and some have not completed the 3-dose series. Recommendations will need to be 

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made for those individuals. Data from the 2vHPV and 4vHPV immunogenicity trials were 

included in the WG’s GRADE evaluation. 

Regarding the GMTs through 60 months of follow-up in one of the 2vHPV trials, for the group 

who received 2 doses on a 0, 6 month schedule at age 9 through 14 years and the group who 

received a 3 dose schedule at 15 through 25 years of age, the antibody kinetics were identical 

in the two groups with the peak titers 1 month after the last dose, a decline, and then plateau at 

about 18 to 24 months [Romanowski, Hum Vaccin 2016]. A similar curve of the antibody 

kinetics has been seen in all of the HPV vaccine trials. 

GMTs through 36 months of follow-up in one of the 4vHPV trials was also shown. In this trial, 

there were 3 groups: a group that received a 0, 6 month schedule at 9 through 13 years of age, 

a group that received a 3-dose schedule at age 9 through 13 years of age and a group that 

received a 3-dose schedule at 16 through 26 years of age. The antibody kinetics were similar in 

the groups with the peak titers one month after the last dose, a decline, and then plateau at 

about 18 to 24 months. The 2-dose group remained higher than the 3-dose women [Adapted 

from: Dobson, JAMA 2013]. 

As discussed during past ACIP meetings, there are no data from RCTs trials of 2- vs 3-doses of 

HPV vaccines evaluating efficacy against infection or disease outcomes. For the 2vHPV, there 

are data from post-hoc analyses of a 3-dose efficacy trial. These were some of the first data 

that stimulated interest in reduced dose schedules. For the 4vHPV, data are available from 

analysis of an interrupted 2- vs 3-dose efficacy trial that was analyzed as an observational 

study. All of these analyses suggest efficacy with less than a 3-dose schedule [Kreimer, Lancet 

Oncol 2011; Kreimer, JNCI 2015; Sankaranarayanan, Lancet Oncol 2016; Markowitz, presented 

at February 2016 ACIP]. 

Post-licensure studies have been used to evaluate other vaccines; however, these types of 

studies are challenging for HPV vaccines at this point in the program. There are 10 published 

studies that have evaluated post-licensure effectiveness by number of doses in settings of a 

recommended 3-dose schedule for 2vHPV or 4vHPV. All of these found that 2 doses were not 

as effective as 3 doses. However, there are many limitations for post-licensure effectiveness 

studies at this time in the vaccination program. First of all, most 2-dose vaccinees had received 

vaccine at a 0, 1 month or a 0, 2 month interval since these studies were in the setting of a 3­

dose recommendation. Persons who received only 2 doses differed from those completing the 

schedule. In some studies, they were older, of lower socioeconomic status (SES), and had 

earlier cervical cancer screening, suggesting differences in exposure to HPV prior to 

vaccination. One study evaluated different intervals between 2 doses, and found that 

effectiveness increased as the interval between doses increased [Herweijer, 2014; DominiakFelden 2015; Blomberg, 2015; Gertig, 2013; Crowe, 2014; Brotherton, 2015; Kavanagh, 2014; 

Cuschieri, 2016; Hofstetter, 2016; Pollock, 2014; Oliver, presented at June 2016 ACIP]. 

The WG’s conclusion is that there are many challenges for vaccine effectiveness evaluations in 

the context of a 3-dose program. Data from these effectiveness studies may not be directly 

applicable to the currently policy question of a 2-dose recommendation due to differences in age 

at vaccination, the interval between the 2 doses, and differences in population in the populations 

receiving 2 doses and 3 doses in these studies. The WG did not include post-licensure 

effectiveness evaluations in its GRADE evaluation. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

To examine different aspects of shifting to a 2-dose schedule, results were considered from 

health economic models. The model used was an individual-based transmission-dynamic 

model. This model takes into account the direct effects of vaccination, as well as herd immunity 

effects. This model uses a variety of inputs and includes 6 important components: 

demographics, sexual behavior and HPV transmission, natural history, vaccination, screening 

and treatment of cervical lesions and cervical cancer, and economics. The objective was to 

evaluate the population-level effectiveness and cost-effectiveness of a 3-dose versus 2-dose 9­

valent vaccination program in the US. 

To summarize the modeling results, the conclusions were that if efficacy and duration of 

protection after 2 doses are similar, 2 doses would be cost-saving compared with 3 doses. 

Exploration of important parameters showed that the incremental health benefits and costeffectiveness of a 3rd dose of HPV vaccine depend most on relative duration of efficacy provided 

by a 2-dose versus 3-dose schedule. Vaccination is predicted to reduce HPV-burden of disease 

substantially after any schedule if protection is at least 20 years. A 2-dose vaccination program 

would provide similar population-level health benefits to 3-dose vaccination, unless 2 doses 

provide shorter duration of protection and do not enable higher vaccination coverage. A 3-dose 

vaccination program is predicted to have high incremental cost per Quality Adjusted Life Years 

(QALY) gained of over $118,000 compared to a 2-dose vaccination program, except when 2­

dose protection is less than 20 years [Laprise, JID 2016; Brisson, presented at June 2016 

ACIP]. 

Because duration of protection is found in the model to be the most important parameter 

influencing population impact, the WG reviewed data on duration of protection for HPV vaccines 

with the ACIP during the last meeting. Most of these data came from follow-up of clinical trials. 

In summary of what was presented to ACIP in June 2016, there is no evidence of waning 

protection after a 3-dose schedule to date. Data are available through about 10 years after the 

2vHPV and 4vHPV became available. Longer follow-up, through about 14 years, is on-going in 

some of these studies. Antibody responses are maintained over time after a 3-dose schedule. 

Again, data are available for about 10 years for 2vHPV and 4vHPV. Longer follow-up, through 

14 years, is on-going in some studies. Waning of detectable antibody to HPV 18 by competitive 

luminex immunoassay (cLIA) in 4vHPV v is not associated with loss of protection. For 2-dose 

schedules, long-term protection data are not available yet from 2-dose trials. However, antibody 

kinetics shown earlier are similar between 2-dose and 3-dose schedules with 2vHPV and 

4vHPV , which suggests that duration of protection will be very similar for a 2-dose and 3-dose 

schedule [Markowitz, presented to June ACIP 2016]. 

Evidence was evaluated using GRADE and was presented to ACIP in June 2016. The main 

policy question was: “Should 2 doses of any HPV vaccine be recommended for 9 through 14 

year-olds?” The population was girls and boys aged 9 through 14 years. The intervention was 

2 doses of HPV vaccine separated by 6 to 12 months. The comparison was 3 doses of HPV 

vaccine at 0, 1–2, and 6 months among women in the age group in which efficacy has been 

demonstrated. The outcome was immunogenicity. 

For the GRADE summary, for 2 doses of HPV vaccine in girls or boys aged 9 through 14 years 

compared with 3 doses of HPV vaccine in women about 15 through 26 years of age, the age 

group in which clinical efficacy was demonstrated, data were available on immunogenicity 

outcomes for 9vHPV vaccine from 1 study, 4vHPV from 2 studies, and 2vHPV from 4 studies. 

All of these studies found evidence of non-inferior immunogenicity with 2 doses. These were 

observational studies, because it was not possible to randomize participants in two different age 

groups. The overall evidence type is 3. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

For the summary of considerations for formulating recommendations, if benefits are expected to 

be the same and the potential AEs are lower, the balance of benefits over harms is greater. 

Again, the evidence type for benefits was type 3. The workgroup placed a high value on 

programmatic considerations, as well as prevention of outcomes due to HPV vaccine types. A 

2-dose schedule is likely to be cost-effective compared to 3 doses. The proposed 

recommendation is a Category A. The specific recommendation language follows in Dr. Meites’ 

presentation. 

Dr. Markowitz briefly mentioned some programmatic considerations. In terms of vaccine 

coverage from 2006-2015, in spite of HPV vaccine recommendations for females being 

published around the same time as those for Tdap and quadrivalent meningococcal conjugate 

vaccine (MenACWY), HPV vaccination coverage in females has increased at a comparatively 

slow pace. Coverage for at least 1 and 3 dose among females has reached 62% for 1 dose and 

42% for 3 doses. Coverage among males began to increase after 2011 when the routine 

recommendation was made for males. In 2015, it was 50% for at least one dose and 28% for 3 

doses [Reagan-Steiner MMWR 2016]. A variety of efforts are ongoing to increase coverage, 

and these have been reviewed with ACIP in the past. 

It is unknown how a 2-dose recommendation would impact vaccination initiation or series 

completion in the US, although it is generally thought that a 2-dose schedule would be easier to 

implement and would be more acceptable. Many other countries have switched to a 2-dose 

schedule. Most of these have school-based vaccination and many already had high coverage, 

so information may not inform the situation in the US. In the US, a 2-dose 0, 6-12 month 

schedule would allow flexibility and vaccinations could coincide with preventive health care 

visits. 

Examination of current coverage data can provide information on the impact of a potential 

change in recommendation on current coverage estimates, and also on the need for 

recommendations that address incomplete schedules. In terms of the percentage of girls and 

boys who received 3, 2, and 1 doses as determined in the 2015 National Immunization SurveyTeen (NIS-Teen), about 10% to 11% received only 2 doses and an additional 10% to 11% 

percent received only 1 dose. Recommendations will need to be made for these individuals as 

well. With regard to the interval in months between the first and second dose among teens who 

started the HPV vaccination series before age 15 years in the US, most received a second dose 

close to the recommended interval of 2 months in the current 3-dose schedule. These data 

include persons who completed a 3-dose schedule as well as those who did not. When looking 

at teens who completed only 2 doses, there is a slightly different picture. Among teens who 

received 2 doses only and the percent who received 2 doses only both at least 5 months apart 

and started the series before age 15, 10.6% of 13 through 17 year olds received only 2 doses, 

and 5.4% received only 2 doses at least 5 months apart and started the series before age 15 

years [NIS-Teen, United States, 2015]. If ACIP votes to accept a 2-dose schedule, these 

individuals could be considered fully vaccinated, and the other 2-dose vaccinees would be 

recommended to receive a third dose in this age group. 

In summary, although three HPV vaccines are licensed for use in the US, after the end of 2016 

only 9vHPV will be available in the US. In October 2016, FDA approved 9vHPV as a 2-dose 

series for persons aged 9 through 14 years. During the past year, ACIP has been reviewing 

data related to 2-dose schedules, including immunogenicity, post-hoc analyses of efficacy trials, 

post-licensure effectiveness, health economic models, and duration of protection. Importantly, 

trials of all HPV vaccines found that the antibody response after 2 doses at 0, 6 months or 0, 12 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

months in 9 through 14 year olds is non-inferior to the response after 3 doses in the group in 

which efficacy was demonstrated. Post-licensure studies examining HPV vaccine effectiveness 

by number of doses are difficult to interpret at this time in the vaccination program. Data from 

follow-up of 3-dose vaccine trials show that duration of protection after HPV vaccination is long 

lasting. Data from follow-up of immunogenicity trials suggest that duration of protection will be 

the same after 2-dose and 3-dose schedules. ACIP used GRADE to evaluate evidence on 2­

dose HPV vaccination schedules. The HPV Vaccines WG proposes a Category A 

recommendation for a 2-dose schedule for persons initiating the series at age 9 through 14 

years. A 2-dose HPV vaccination schedule might facilitate vaccine initiation and series 

completion in the US. 

Proposed Recommendations for 2-Dose HPV Vaccination 

Elissa Meites, MD, MPH 

Medical Epidemiologist 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Meites reminded everyone that three HPV vaccines are licensed for use in the US: 2vHPV, 

4vHPV, and 9vHPV. Recently, on October 7th, 9vHPV was approved by the FDA for use in a 2­

dose series for girls and boys at ages 9 through 14 years. The current ACIP recommendations 

are as follows: 

 HPV vaccine is recommended for routine vaccination at age 11 or 12 years. The 

vaccination series can be started beginning at age 9 years. 

 ACIP also recommends HPV vaccination for: 

 Females aged 13 through 26 years not vaccinated previously, 

 Males aged 13 through 21 years not vaccinated previously* 

 Immunocompromised persons (including those with HIV infection) and men who 

have sex with men through age 26 years, if not vaccinated previously 

* Males aged 22 through 26 years may be vaccinated 

The rationale for the vote during this session is that HPV vaccines are highly effective and safe, 

and a powerful prevention tool for reducing the burden of HPV infections and associated 

disease; evidence suggests that a 2-dose schedule (administered at 0, and 6–12 months) will 

have efficacy equivalent to a 3-dose schedule (administered at 0, 1–2, and 6 months) if the HPV 

vaccination series is initiated before the 15th birthday. 

Here is the outline of the proposed recommendations that would be included in a Policy Note: 

 Routine and catch-up age groups (no changes) 

 Dosing schedules 

 Persons with prior vaccination 

 Interrupted schedules 

 Special populations 

 Medical conditions 

 Contraindications and precautions (no changes) 

 Summary 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

No changes are proposed to the routine and catch-up age groups for HPV vaccination. Major 

additions are proposed to the sections on dosing schedules and persons with prior vaccination. 

Clarifying language is proposed for the sections on interrupted schedules, special populations, 

and medical conditions. For contraindications and precautions, no changes are proposed. The 

summary includes the proposed recommendation category. 

The routine and catch-up age groups, for whom HPV vaccination is recommended, would not 

change. The text of this section would continue to emphasize that: 

 ACIP recommends routine HPV vaccination for girls and boys at age 11 or 12 years.

Vaccination can be given starting at age 9 years.

 ACIP also recommends vaccination for females through age 26 years and for males

through age 21 years who were not adequately vaccinated previously. Males aged 22

through 26 years may be vaccinated.

 Additional details will be presented in the sections on Special Populations, and Medical

Conditions.

Beginning with the section on dosing schedules, underlined text indicates new information or 

changes to the current recommendations. Based on the evidence previously presented to ACIP 

on 2-dose immunogenicity, efficacy, cost-effectiveness, duration of protection, GRADE 

evaluation, and additional considerations, the proposed dosing schedules for HPV vaccination 

are: 

 For persons initiating vaccination before the 15th birthday, the recommended

immunization schedule is 2 doses of HPV vaccine. The second dose should be

administered 6–12 months after the first dose (0, 6–12 month schedule).*

 For persons initiating vaccination on or after the 15th birthday, the recommended

immunization schedule is 3 doses of HPV vaccine. The second dose should be

administered 1–2 months after the first dose, and the third dose should be administered

6 months after the first dose (0, 1–2, 6 month schedule).* 

* See footnote defining minimum intervals

The next section with major changes is on evaluating persons with prior vaccination. This is a 

new section proposed to address questions about persons who have received any HPV vaccine 

in the past. The proposed text is: 

 Persons who initiated vaccination with 9vHPV, 4vHPV, or 2vHPV before the 15th

birthday, and received 2 doses at the recommended dosing schedule, or 3 doses at the

recommended dosing schedule, are considered adequately vaccinated.

 Persons who initiated vaccination with 9vHPV, 4vHPV, or 2vHPV on or after the 15th

birthday, and received 3 doses at the recommended dosing schedule, are considered

adequately vaccinated.

In addition, this section could formalize current CDC supplemental guidance for vaccination 

providers which appears online at: www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf. This 

states that 9vHPV may be used to continue or complete a series started with 4vHPV or 2vHPV. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Furthermore, the workgroup would like to include an explicit statement that for persons who 

have been adequately vaccinated with 2vHPV or 4vHPV, there is currently no ACIP 

recommendation regarding additional vaccination with 9vHPV. 

In the section on interrupted schedules, the following is proposed: 

 If the vaccine schedule is interrupted, the vaccination series does not need to be 

restarted. 

 Number of recommended doses is based on age at administration of the first dose. 

Before presenting the proposed minimum intervals, Dr. Meites reviewed the current 

recommendations and evidence considered on this topic. In current guidelines, the minimum 

interval between the 1st and 3rd dose in a 3-dose series is given at 24 weeks, slightly less than 6 

months. The WG noted that in both the new 2-dose and the original 3-dose trials of 9vHPV, 

doses given at a target 6-month interval were scheduled for 180 days after the first dose, which 

is equivalent to 26 weeks. However, participants were included if they received vaccine within 4 

weeks of this target date, and many participants in the 2-dose trial did receive their second dose 

in this window. Therefore, the 9vHPV trial data support a minimum interval of 5 months, which 

is equivalent to 22 weeks. Furthermore, the updated FDA-approved label for 9vHPV vaccine 

states a minimum interval of 5 months between doses in a 2-dose series. For these reasons, 

the WG proposed that a footnote defining the minimum intervals include the following: 

 In a 2-dose series of HPV vaccine, the minimum interval is 5 months between the 

first and second dose. 

 In a 3-dose series of HPV vaccine, the minimum intervals are: 

1 month between the first and second doses, 

3 months between the second and third doses, and 

5 months between the first and third doses. 

 A vaccine dose administered at a shorter interval should be re-administered at 

the recommended interval. 

The section on special populations is largely unchanged. Currently, for children with a history of 

sexual abuse or assault, ACIP recommends routine HPV vaccination beginning at age 9 years. 

In addition, ACIP currently recommends an extended catch-up age range for MSM, and for 

immunocompromised persons. The WG proposed to add clarifying text to the current guidance 

that defines these populations more clearly. 

To the current recommendation for MSM, the proposed clarification would add terms that are 

used elsewhere to recognize diversity in sexuality and gender identity and expression among 

men whose behavior may include sex with men. The proposed text is: 

 For gay, bisexual, and other men who have sex with men (MSM), ACIP recommends 

routine HPV vaccination as for all adolescents, and initiation of vaccination through age 

26 years for those who were not adequately vaccinated previously. For transgender 

persons, ACIP recommends HPV vaccination through age 26 years for those who were 

not adequately vaccinated previously. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

For immunocompromised persons, the WG did not feel that a 2-dose schedule should be 

recommended for all types of immunocompromise. The purpose of this addition is to clarify 

which immunocompromising conditions should continue to receive 3 doses, based on expert 

opinion and consistent with the Infectious Disease Society of America (IDSA) clinical practice 

guidelines for vaccination of the immunocompromised host. The current recommendation with 

the full text of the proposed clarifying addition and footnote is: 

 ACIP recommends HPV vaccination for immunocompromised females and males aged 

9 through 26 years with three doses of HPV vaccine (0, 1–2, 6 months). Persons who 

should receive 3 doses are those with primary or secondary immunocompromising 

conditions that might reduce cell-mediated or humoral immunity, such as B lymphocyte 

antibody deficiencies, T lymphocyte complete or partial defects, HIV infection, malignant 

neoplasm, transplantation, autoimmune disease, or immunosuppressive therapy, since 

immune response to vaccination may be attenuated.

* 

* The recommendation for a 3-dose schedule does not apply to children aged <15 years 

with asplenia, asthma, chronic granulomatous disease, chronic heart/liver/lung/renal 

disease, CNS anatomic barrier defects (e.g., cochlear implant), complement deficiency, 

diabetes, or sickle cell disease. 

Finally, contraindications and precautions, including those related to pregnancy, are unchanged 

from previous recommendations. Standard language is included on the Vaccine Adverse Event 

Reporting System (VAERS). Reports can be submitted to VAERS online, by fax, or by mail. 

Additional information about VAERS is available by telephone (1-800-822-7967) or online 

(https://vaers.hhs.gov). 

To summarize, the proposal is for ACIP to recommend a 2-dose schedule of HPV vaccine for 

girls and boys who initiate the vaccination series at ages 9 through 14 years. The proposed 

category is a Category A recommendation, for everyone in this age range. As discussed in this 

presentation, the WG proposed text for each of the sections shown here, for ACIP to consider: 

 Routine and catch-up age groups (no changes) 

 Dosing schedules 

 Persons with prior vaccination 

 Interrupted schedules 

 Special populations 

 Medical conditions 

 Contraindications and precautions (no changes) 

 Summary 

In terms of next steps, the WG anticipates that a Policy Note could be published in the MMWR 

before the end of this year, and detailed methods and GRADE tables would be linked and 

posted online. 

Discussion Points 

Regarding the 6 to 12 month interval and how this may play out in the real world, Dr. Szilagyi 

pointed out that education for pediatricians and family physicians is important. He suspects that 

many practitioners will bring adolescents back at their next well-child visit. There is one 

complication with that in that some commercial insurance plans will not pay for a well-child visit 

if it is within 12 months. That does not include Medicaid or public health insurance, so he did 

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not know what percentage of the population that would include, but thought that it would be 

small but measurable. That means that many practitioners may bring their adolescents back at 

13, 14, or 15 months. 

Dr. Hunter asked about the current rates of 1-dose vaccination amongst 9 through 14 year olds, 

especially in comparison to whether that is higher than the current rates of 3-dose vaccination 

amongst 15 through 26 year olds to understand how much rates may bump up. Dr. Markowitz 

replied that those are not the age groups in NIS-Teen, but Dr. Wharton could provide additional 

information. 

Dr. Messonnier added that there may be people who are not initiating the series because of the 

complicated schedule. While this question can be answered based on who is getting the 

vaccine now, the hope is that by simplifying the regimen, more people will access it and this will 

help providers make a stronger vaccine recommendation. Dr. Wharton indicated that reported in 

the most recent publication of NIS-Teen, was that 3-dose coverage in the 13 to 15 year old age 

group, which corresponds to the Healthy People 2020 target, coverage was pretty low at 27% 

coverage in males and 37% coverage in females. She emphasized the point that Dr. 

Messonnier made, that a recommendation for a 2-dose series at younger ages might very well 

result in better completion than with the current recommendation. 

Ms. Pellegrini stressed that the 0, 2, 6 month schedule is very hard for families with teenagers. 

Going to the pediatrician 3 times in 6 months is very difficult. The more flexible schedule and 

wider interval proposed would allow for the next well-child visit, sports physical, or sick visit 

could make a real difference in increasing the completion rates in a timely fashion and in 

incentivizing families to begin the schedule. There are people who look at the 0, 2, 6 schedule 

and say they know they cannot do it and will not start it. 

Dr. Lett (AIM) heard that ACIP would not be considering recommendations to change the 

wording of the age at which to begin HPV vaccine in this statement. She asked if there was any 

other permissive use language that could be considered including in the statement about 

starting the vaccination earlier. 

Dr. Bennett emphasized that the goal for this session was to focus on the 2-dose schedule; 

however, the WG does intend to reassess the language around the recommended age 

parameters downward and upward (within the 9 through 26 year age range). That probably will 

be brought back at a later time. 

Referring to Slide 9 regarding persons with prior vaccination, Dr. O’Leary (PIDS) thought the 

wording might be confusing. The statement in the first bullet might be interpreted by providers 

as the old recommended schedule of 2 doses at 0 and 1-2 months. He suggested specifying 

the number of months so providers understand whether it indicates the old schedule (0, 1-2, 6 

months) versus the newly recommended schedule (0, 6-12 months). 

Dr. Gemmill (NACI) reported that while Canada took a different route, they came to the same 

position in time. They went to a 2-dose schedule with the 4vHPV vaccine, and are now 

discussing for future consideration the same thing ACIP was discussing during this session. He 

thought he heard stated that anybody who had 2 or 3 doses with any vaccine is considered to 

be completely immunized. Inevitably, some people who have had 2vHPV+ or 4vHPV will want 

protection from the other types. He asked whether there would be a permissive 

recommendation that would allow for this and, if so, what it would be. Canada is struggling with 

this. 

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Dr. Meites replied that the current proposal includes the language that, for those who have been 

adequately vaccinated previously, there is no ACIP recommendation regarding additional 

vaccination with 9vHPV. 

Referring to Slide 13 regarding minimal intervals, Dr. Walter pointed out that the third bullet may 

need further clarification: “A vaccine dose administered at a shorter interval should be readministered at the recommended interval.” For example, if someone gave a vaccine at 0 and 4 

months, he would assume that would mean the next dose should be given at 5 months. 

However, someone might assume that this meant 6 from the dose given at 4 months. 

Dr. Meites pointed out that the text on Slide 13 was abbreviated to avoid distracting from the 

main presentation, and explained that the full text of the footnotes (shown on Slide 27) would 

include full details about the recommended minimum intervals between each dose for both 2­

dose and 3-dose schedules, along with guidance on re-administration of an early dose. 

Dr. Hayes (ACNM) said she thought there was an International Classification of Diseases (ICD)­

10 code so that a well-child visit does not have to be coded in order to give the vaccine. She 

said she loved the liberal language about recommended time frames for giving the vaccine, in 

that if the child presents late it can still be given. When administering the vaccine at family 

planning visits at the same time as giving Depo-Provera, her colleagues were unclear about 

whether a second dose of vaccine could be given a year later. 

Dr. Messonnier pointed out that a number of complicated clinical decision issues could come 

from this policy change. CDC will try to work through all of those with the professional 

organizations. She requested that any questions be submitted to Dr. Wharton, and CDC will try 

to ensure that they are included in the massive health communication materials that CDC will 

develop to help clinicians work their way through this. 

Referring to Slide 9, Dr. Hahn (CSTE) commented that someone she knows has had the first 2 

doses at 2 months apart, and she suggested that it read “and received 2 doses at least 5 

months apart” to be more clear. 

Dr. Middleman (SAHM) read the following statement into the record: “Members from the 

Society for Adolescent Health and Medicine, including the Vaccination Committee and the 

President-elect and current President have significant concerns regarding the new policy’s use 

of the labels “gay” and “bisexual” as proxies for behavior that places men 22 to 26 years of age 

at increased risk of HPV acquisition. Labels that characterize sexual orientation do not 

necessarily characterize behavior. If a behavior puts a person at greater risk for disease and 

greater need for vaccination, then it is more accurate to describe the specific behavior, for 

example “men who may have or have had sex with men.” Men who identify as gay or bisexual 

may not engage in behaviors that place them at increased risk for HPV acquisition and 

conversely, men who do not identify as gay or bisexual may engage in sexual behaviors that 

place them at increased risk. Importantly, many HCP do not routinely screen their patients in 

great detail regarding sexual orientation or sexual behaviors. The evolving nature of sexual and 

gender expression makes generalizing with the use of labels obsolete and inaccurate. We 

potentially miss vaccinating many young men who should be protected against disease. 

Furthermore, we know from past experiences, as Dr. Schaffner noted earlier today, that 

targeting vaccination for specific groups has not been an effective public health strategy. The 

most inclusive and effective strategy to protect young men is to avoid assumptions based on 

generic labels. We recommend: 1) eliminate imprecise labels from vaccination 

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recommendations that falsely assume an equivalence between sexual orientation and risk 

behaviors, potentially resulting in missed opportunities for vaccination; and 2) update the 

recommendations for young men, hopefully at the next meeting, to include catch-up for all 22 to 

26 year olds in order to protect all young men, including those whose behaviors defy labels, 

from the morbidity and mortality associated with HPV infection. We have an extremely effective 

vaccine that is more cost-effective than initially predicted. The number of vaccines distributed 

for 22 to 26 year old males is reportedly extremely low, implying poor uptake among this group 

of men. The goal for our young men at this point should be to use fewer labels, make fewer 

assumptions, have fewer restrictions, and strive to be more inclusive, immunize more men, and 

save more lives. Thank you.” 

Dr. Meites thanked Dr. Middleman for her commitment to this issue and her work with 

adolescent patients. She stressed that it certainly was the intent of the proposal to make the 

language inclusive of the populations who should receive vaccine. As far as the particular 

phrasing of the terms, she pointed out that these terms are widely used at CDC. She showed 

an assortment of websites from different CDC programs that focus on lesbian, gay, bisexual, 

and transgender (LGBT) health. She pointed out that the language included in the CDC fact 

sheet on “HPV in Men,” under the heading “Can I get an HPV vaccine?” already specifically 

includes, “Gay, bisexual, and other men who have sex with men.” Dr. Meites explained that the 

focus for this session was to propose formalizing the language already in use to describe the 

existing ACIP recommendation for MSM. As mentioned, the topic of recommendation language 

over the full age range for which HPV vaccine is licensed (i.e., for males ages 22 through 26 

years) is a topic that the WG would like to continue discussing in the future. 

Dr. Messonnier thanked the HPV WG and expressed appreciation for SAHM’s concern, 

recognizing that SAHM is an incredibly important partner for this age group and on this vaccine. 

CDC wants to find a way to make this work. The WG came to this language as everyone heard, 

but outside of the bullet, there is clinical language that CDC uses in its health communication 

materials that derive from the kind of conversations they have, but the wording is not always 

exactly what is voted on. CDC commits to SAHM that the agency will engage with the experts 

who are putting out this information to try to find something that is acceptable to SAHM and also 

meets the purpose of the WG, which is actually to be more inclusive, not less inclusive. 

Dr. Middleman (SAHM) expressed her appreciation, and said that SAHM appreciates the 

opportunity to contribute. 

Dr. Bennett thanked Dr. Middleman for raising this important issue. 

Referring to Slide 13 regarding minimum intervals, Dr. Wexler (IAC) pointed out that this was a 

divergence from how CDC usually writes recommendations for spacing minimum intervals. 

Usually, ACIP would say 4 weeks instead of 1 month and 12 weeks instead of 3 months. 

Language in the childhood schedule says, “For purposes of calculating intervals between doses, 

4 weeks equals 28 days. Intervals of 4 months or greater are determined by calendar months.” 

That is, 4 months is the cutoff for using month terminology. 

Dr. Meites said it was also her understanding that these were used interchangeably. Since 

preferable, she expected the WG would be supportive of using the terms “4 weeks” and “12 

weeks” rather than the terms “1 month” and “3 months.” 

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Dr. Offit (Children’s Hospital Philadelphia) said that while he understood that there was no 

additional recommendation for those who have completed either the 2vHPV or 4vHPV series, it 

was not clear to him why. There is a 9vHPV vaccine that will protect against an additional 

several thousand cases of cancer and presumably hundreds of deaths. One could argue that 

the best medical recommendation is for someone who has completed either 2vHPV or 4vHPV 

to get 2 doses of 9vHPV vaccine separated by at least 6 months. That would save lives. He 

asked whether the reason the WG was not making that recommendation was programmatic or 

financial. Dr. Markowitz replied that this had not been brought before the entire ACIP, and for a 

variety of reasons was not part of the earlier recommendations. However, the WG may revisit 

this discussion going forward. 

Regarding Slide 15 on special populations, Dr. Thompson (NVAC) said she did not understand 

why there was different language used for these different populations of gay, bisexual, and 

other MSM and transgender individuals. The language in the slide differed in a way that did not 

make sense to her, and she wondered what the rationale was for the actual language on which 

the committee would be voting. That is, why was vaccination for all adolescents recommended 

for the first group but not the second? She also wondered about the language for proposed 

medical conditions in terms of what evidence there is about the 3-dose schedule in these 

special populations with respect to the timing. Is it better for these individuals to have the 0, 1-2, 

and 6 month schedule or 0, 6 to 12 month and then a booster later. If this is not known, she 

asked whether any research is being done to figure out the right timing for immunocompromised 

populations. 

Dr. Meites replied that the language in the two sentences on Slide 15 originally was one 

sentence, and the WG revised it into two sentences for clarity. They certainly could repeat, 

“ACIP recommends routine HPV vaccine as for all adolescents” in the second sentence. 

Dr. Cohn said that she wanted to make it clear that the proposed recommendation from the WG 

was solely about the 2 doses, and that all of the clinical guidance language they were seeing 

could be modified before publication of the MMWR. 

Regarding Dr. Thompson’s second question on the timing of the 3-dose regimen for those who 

are immunocompromised, Dr. Meites referred to Slide 28. She pointed out that it is known that 

HPV vaccines are non-infectious. The concern is that the immune response following 

vaccination may be attenuated in persons with certain immunocompromising conditions; that is, 

they might produce lower GMTs and antibody responses if their cell-mediated or humoral 

immune responses are reduced. As far as the timing of doses, she said she was not aware of 

any studies that have evaluated a 6 to 12 month schedule in immunocompromised patients. 

For these reasons, the standard 3-dose recommendation has been left in place for these 

persons as well as for those who initiate the vaccine series as an older teen. 

Dr. Maldonado (AAP) indicated that COID met to discuss the proposed wording. COID strongly 

supports the 2-dose recommendation, taking into account the other issues that were brought up 

around operational issues, opportunities for missed second doses, et cetera. In particular, one 

of the areas that COID is concerned about and would recommend some thoughtful 

consideration is expanding to the larger age range for the purposes of including optimal 

vaccination periods for younger children. 

Requesting that Slide 27 with the full footnotes for minimum intervals be redisplayed, Dr. Lett 

(AIM) asked if the proposed minimum interval was 4 months. 

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Dr. Meites indicated that this slide articulates the proposed minimum intervals and proposed 

language about what to do if a vaccine dose has been administered at an interval that was 

shorter than that. The proposal was, in a 2-dose schedule, “If the second dose is administered 

at a shorter interval, an additional dose should be administered at least 4 months later,” and in a 

3-dose schedule, “If a vaccine dose is administered at a shorter interval, it should be readministered after another minimum interval.” 

Dr. Lett (AIM) emphasized that this would be important for individuals who had not had their 

vaccines on time. 

Public Comments 

Christina Hildebrand 

A Voice For Choice Advocacy 

I agree with dosing going down to 2. My concern, and I know this isn’t your choice, but with the 

9vHPV vaccine being the only one available, the increase in aluminum is double for every dose. 

That is a concern, and I wonder if the safety studies have been done surrounding the aluminum 

specifically and looking at things like premature ovarian failure and other adverse reactions that 

have been reported, and looking at the long-term. I know that the 2-dose brings it down, but it’s 

still higher than the 3-doses of the initial 4- or 2-variant GARDASIL®. 

Dr. Bennett thanked Ms. Hildebrand for her comments and referred her to the SMEs and CDC‘s 

vaccine safety personnel to discuss that issue. 

Kristen Morelli 

Richmond, Rhode Island 

Submitted Via Email to be Included in the Record 

I am deeply concerned about the safety, effectiveness, and necessity for the HPV vaccine for 

the following reasons. 

•	 Concern was publicly raised about ovarian failure related to the HPV vaccine. This 

should not be ignored and further detailed studies should be done immediately, and prior 

to more vaccines being recommended. 

•	 Advertising the HPV vaccine for cancer prevention should cease immediately. Not one 

study proves cancer prevention, it is an assumed result that does not have solid proof 

yet. This is extremely misleading to the public and does not permit proper informed 

consent. 

•	 CDC should cease and desist on any form of advertising of any vaccines to the public. 

Vaccine manufacturers are free from liability when a vaccine causes a negative side 

effect. They benefit full profits of all vaccine sales. Our tax dollars and government 

agencies should not be paying to advertise a product that produces billions in profits for 

the manufacturer. 

•	 Multiple countries are no longer recommending the HPV vaccine due to a high level of 

young adults having serious side effects of the vaccine. The CDC and ACIP need to take 

this seriously and show the US public that they do care about the youth, and will also do 

more follow up studies and further investigation of the HPV vaccine. 

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0 Opposed: N/A
 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

The fact that vaccine manufacturers are not liable in a similar fashion to all other pharmaceutical 

manufacturers is also a big concern for me. These ARE pharmaceuticals, being shot into the 

veins of small children. Testing should be as thorough as any other pharmaceutical. 

Vote: 2-Dose HPV Vaccination Recommendations 

Dr. Kempe motioned to approve the proposed 2-Dose HPV Vaccination Recommendations. Dr. 

Lee seconded the motion. The motion carried unanimously with 13 affirmative votes, 0 negative 

vote, and 1 abstention. The disposition of the vote was as follows: 

13 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Stephens, Szilagyi, Walter
 

1 Abstained: Romero (due to non-vaccine-related
 

VFC Resolution 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Santoli explained that the purpose of this resolution was to reflect the new dosing schedules 

for HPV vaccine. Eligible groups include all children 9 through 18 years of age. ACIP 

recommends routine HPV vaccination at age 11 or 12 years, and vaccination can be given 

starting at age 9 years. ACIP also recommends vaccination for females and males aged 13 

through 18 years who were not adequately vaccinated previously. The table below summarizes 

the recommended number of HPV vaccine doses and schedule for specific groups of children: 

0, 6–12 months1 Persons initiating vaccination at age 

9 through 14 years, except 

immunocompromised persons2 

0, 1–2, 6 months3 Persons initiating vaccination at age 

15 through 18 years, and 

immunocompromised persons2 

initiating vaccination at 9 through 18 

years 

 doses 

Population 

2 

3 

Table Notes: 

1. In a 2-dose schedule of HPV vaccine, the minimum interval is 5 months between the first and the second dose. 

2. Persons with primary or secondary immunocompromising conditions that might reduce cell-mediated or humoral 

immunity. 

3. In a 3-dose schedule of HPV vaccine, the minimum intervals are 1 month between the first and second dose, 3 months 

between the second and third dose, and 5 months between the first and third dose. 

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Recommended 

number of

Recommended 

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Recommended Dosage 

Contraindications and Precautions 

0 Opposed: N/A
 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Persons who initiated vaccination with 9vHPV, 4vHPV, or 2vHPV before the 15th birthday, and 

received 2 doses at the recommended dosing schedule, or 3 doses at the recommended dosing 

schedule, are considered adequately vaccinated. Persons who initiated vaccination with 

9vHPV, 4vHPV, or 2vHPV on or after the 15th birthday, and received 3 doses at the 

recommended dosing schedule, are considered adequately vaccinated. Vaccine doses 

administered at shorter than minimum intervals should be re-administered as recommended. 

9vHPV may be used to continue or complete a series started with another HPV vaccine. If the 

vaccine schedule is interrupted, the series does not need to be restarted. 

Refer to product package inserts. 

Contraindications and Precautions can be found in the package inserts available at 

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM093833 

Statement Regarding Update Based on Published Documents 

[If an ACIP recommendation regarding Hepatitis B vaccination is published within 12 months 

following this resolution, the relevant language above (except in the eligible groups sections) will 

be replaced with the language in the recommendation and incorporated by reference to the 

publication URL.] 

Vote: VFC Resolution for 2-Dose HPV Vaccination Recommendations 

Ms. Pellegrini motioned to approve the VFC Resolution for the 2-Dose HPV Vaccination 

Recommendations. Dr. Walter seconded the motion. The motion carried unanimously with 13 

affirmative votes, 0 negative vote, and 1 abstention. The disposition of the vote was as follows: 

13 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Stephens, Szilagyi, Walter
 

1 Abstained: Romero (due to non-vaccine-related funding support)
 

Meningococcal Vaccines 

Introduction 

David S. Stephens, MD 

Chair, Meningococcal Work Group 

Advisory Committee on Immunization Practices 

Dr. Stephens reminded everyone that a revised dosing schedule was approved for Trumenba®, 

Pfizer Vaccines’ MenB-FHbp vaccine. The dosing schedule was approved by FDA on April 14, 

2016 to change the original language of the 3-dose schedule from 0, 2, and 6 month to 0, 1-2, 

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and 6 months and to approve a 2-dose schedule with administration at 0 and 6 months. The 

revised schedule indicates that the choice and dosing schedule may depend upon the risk of 

exposure and the patient’s susceptibility to serogroup B meningococcal (MenB) disease. 

Dr. Stephens indicated that the presentation topics for this session would include the following: 

 Impact of MenB-FHbp (Trumenba®) on meningococcal carriage 

 Immunogenicity studies of two MenB vaccines in adults 

 MenB-FHbp update 

 Considerations for use of 2- and 3-dose schedules of MenB-FHbp 

 ACIP and VFC votes anticipated 

The policy options for 2- or 3-dose schedules of MenB-FHbp (Trumenba®) are: 

 For persons at increased risk and for use during outbreaks: 

 Preference for 3-dose schedule (0, 1-2, 6 months) 

 When given to healthy adolescents: 

 Preference for 2-dose schedule (0, 6 months) 

OR 

 Option for 2- (0, 6 months) or 3-dose (0, 1-2, 6 months) schedule 

OR 

 Preference for 3-dose schedule (0, 1-2, 6 months) 

Additional WG activities include a Policy Note regarding the recommendations for use of 

meningococcal conjugate vaccines in HIV-infected persons, which is to be published in the 

MMWR on November 4, 2016. The WG is continuing to review additional data on MenB 

vaccines as it becomes available, and considering the issue of booster doses of MenB vaccine 

for persons at increased risk. 

Impact of MenB-FHbp (Trumenba®) on Meningococcal Carriage 

Heidi M. Soeters, PhD, MPH 

Meningitis and Vaccine Preventable Diseases Branch 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

During this session, Dr. Soeters discussed a meningococcal carriage evaluation conducted in 

response to a serogroup B meningococcal disease outbreak and the resulting mass vaccination 

campaign that occurred at a college in Rhode Island. 

In terms of background and context, meningococcal disease most commonly takes the form of 

meningitis or bacteremia. It often starts with influenza-like symptoms but can progress within 

hours to a serious illness that can include high fever, severe headache, stiff neck, confusion, 

and a purpuric rash. This disease has a 10% to 15% case-fatality ratio, even with appropriate 

antibiotic treatment. Of survivors, 11% to 19% have permanent sequelae, such as cognitive 

deficits or amputations due to necrosis of the extremities. Meningococcal disease is caused by 

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the bacterium Neisseria meningitidis, which is a gram-negative diplococcus. Invasive 

meningococci generally have a polysaccharide capsule surrounding the cell, which confers the 

serogroup. Of the 12 different serogroups of meningococci that have been identified, only 6 

primarily cause invasive disease. 

Traditionally, meningococcal vaccines are based on the capsular polysaccharide that is specific 

to each serogroup. Therefore, the resulting protection is serogroup-specific. There are 

polysaccharide vaccines composed of purified capsular polysaccharide. Formulations include 

monovalent A, monovalent C, bivalent A-C, and quadrivalent A-C-W-Y. There also are 

conjugate vaccines, where the capsular polysaccharides are conjugated to proteins, such as 

tetanus or diphtheria toxoids. These vaccines achieve similar or greater immunogenicity and 

duration of protection than polysaccharide vaccines, and are formulated as monovalent A, 

monovalent C, or quadrivalent A-C-W-Y. The conjugate quadrivalent ACWY, or MenACWY, 

vaccine is routinely recommended for adolescents in the US. This same approach of basing a 

vaccine on the capsular polysaccharides has not worked for serogroup B, because the 

serogroup B polysaccharide antigen is similar to human antigens, leading to poor 

immunogenicity and concerns about potential autoimmunity. 

As a result, serogroup B, or MenB, vaccines have to take a different approach and focus on 

outer membrane proteins. These antigens have multiple alleles and variable expression in 

different strains of the bacteria. Not all serogroup B bacteria will express the antigens that are 

present in a particular vaccine, and the serogroup B polysaccharide capsule, which is required 

for virulence, is not contained in MenB vaccines. Unlike vaccines for other meningococcal 

serogroups, MenB vaccines are not expected to be protective against all serogroup B strains in 

circulation. Also, since they are based on outer membrane proteins, and not on the serogroupspecific capsule, they may help protect against other serogroups as well. 

There are two MenB vaccines licensed in the US: MenB-FHbp (Trumenba®) and MenB-4C 

(Bexsero®). MenB-FHbp is a 2-component vaccine, containing a FHbp variant from each 

subfamily A and B. It is given in 2 or 3 doses. Bexsero® is a 4-component vaccine, containing 

NadA, a FHbp from subfamily B, NHBA, and porA and is given in 2 doses. 

In terms of transmission, meningococcal bacteria are carried in the human nasopharynx, and 

most carriers remain completely asymptomatic. Less than 1% of persons exposed to the 

organism develop invasive disease. The bacteria are spread through close contact, specifically 

via respiratory or oral secretions from patients or asymptomatic carriers. Important risk factors 

for both disease and carriage among adolescents include age1,2, social mixing3, and smoking1. 

As the majority of transmission is thought to be attributable to asymptomatic carriers, 

decreasing carriage is the main way to provide herd immunity against meningococcal disease 

[

1Harrison et al. JID 2014. (US); 2Jeppesen et al. J Infect 2015. (UK); and 3Mandel et al. JID 

2013. (US)]. 

Looking at what we know about vaccine impact on meningococcal carriage, in the United 

Kingdom (UK), vaccines targeting serogroup C were shown to decrease nasopharyngeal 

carriage of serogroup C by 66% one year post-vaccination, thereby decreasing transmission 

and providing herd protection1. MenA conjugate vaccine nearly eliminated serogroup A 

carriage2,3. The understanding of MenB vaccine impact on carriage is currently limited. The 

only previous study was conducted using MenB-4C, and found an 18% reduction in carriage of 

any meningococcal bacteria, and no effect specifically on serogroup B carriage by 3 months 

after completion of the 2-dose series4. To date, no data has been published regarding the effect 

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of MenB-FHbp on carriage [1Maiden et al. Lancet (2002); 2 Daugla et al. Lancet (2014); 3 

Kristiansen et al. CID (2013); 4Read et al. Lancet (2014)]. 

 

 

 

 

 

 

 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

In the US, 3 serogroups (B, C, and Y) are the primary causes of meningococcal disease. This 

graph shows the incidence of these serogroups in adolescents and young adults following the 

introduction of conjugate MenACWY vaccine in 2005: 

While incidence of all serogroups is low, serogroup B (in black) is the leading cause of 

meningococcal disease in this age group. In fact, serogroup B caused 7 outbreaks on college 

campuses since 2009, resulting in 41 cases and 3 deaths [Source: NNDSS data with additional 

serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments. 

Unknown serogroup (21%) and other serogroups (7%) excluded]. 

To provide some background on this particular outbreak at Providence College in Rhode Island, 

2 cases of serogroup B occurred in undergraduate students on January 31 and February 5, 

2015. The cases resided in different dormitories and had no known epidemiologic links. Both 

were determined to have a rare sequence type, ST-9069, never before seen in the US. Both 

case-patients survived. These 2 cases among a population of 4500 students indicated an 

attack rate of 44 cases per 100,000, nearly 500 times higher than the national incidence among 

persons aged 17 through 22 years. In response to the outbreak, Providence College rapidly 

implemented a mass vaccination campaign using MenB-FHbp. The three doses were provided 

in February, April, and September of 2015, with remarkably high vaccination coverage of 94% 

with the first dose, 80% with the second, and 77% with the third. Incoming freshman in the fall 

of 2015 also were offered to begin the series. 

CDC incorporated a meningococcal carriage evaluation into this vaccination campaign. It had 2 

objectives, which were to: 1) determine the baseline prevalence of nasopharyngeal carriage of 

Neisseria meningitidis, and 2) assess the impact of MenB-FHbp vaccination on carriage. The 

evaluation consisted of a short questionnaire assessing risk factors for meningococcal carriage 

and disease, followed by an oropharyngeal swab. All undergraduate students at Providence 

College and graduate students who lived on campus were eligible to participate. Specimens 

were evaluated using culture, slide agglutination, real-time polymerase chain reaction (rt-PCR), 

and whole genome sequencing. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

As mentioned, 2 methods were used to determine the serogroup of each isolate: rt-PCR and 

slide agglutination. PCR is a genotypic test that detects the presence of capsule biosynthesis 

genes for each serogroup, regardless of whether they are expressed. PCR can detect 

serogroups A, B, C, W, X, and Y and any specimen that does not contain the genes for one of 

these serogroup capsules is considered non-groupable. Slide agglutination, on the other hand, 

is a phenotypic test which uses antiserum to look for expression of each serogroup, and can 

detect the same 6 serogroups as PCR, in addition to serogroups E and Z, which rarely cause 

invasive disease. Any specimen that does not clump with the antiserum for any of the 

serogroups is considered non-groupable according to slide agglutination. Meningococcal 

bacteria can possess the genes for a serogroup but not be expressing them in their current 

environment, which would produce discordant results according to these 2 methods. Therefore, 

both methods were used in conjunction to get a more precise picture of meningococcal 

dynamics in this setting. 

Additionally, meningococcal vaccination records were abstracted for each participant, recording 

the doses and dates of previous MenACWY or MenB vaccination. This process was repeated 4 

times, resulting in 4 cross-sectional snapshots of carriage on-campus. Round 1 occurred in 

February 2015, the week after the outbreak and dose 1 clinics. Round 2 occurred in 

conjunction with dose 2 in April. Round 3 occurred in September, as upperclassmen received 

dose 3 and incoming freshmen received dose 1. Round 4 occurred one year post-outbreak, 

including fully vaccinated upperclassmen and freshmen receiving dose 3. 

For analysis, descriptive statistics were performed on participant characteristics. The proportion 

of students were assessed in terms of overall meningococcal carriage and specifically 

serogroup B carriage, and how this changed over time. Prevalence ratios were estimated using 

general estimating equation methods for repeated measures. Finally, as a number of students 

participated in multiple rounds, within-individual changes in carriage over time are being 

examined. 

The number of participants in each round ranged from 622 to 878. In total, 2843 swabs were 

collected from 2014 unique individuals. This table shows participant characteristics across the 4 

rounds: 

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Note that as the evaluation took place across 2 academic school years, the class of 2019 was 

only included in rounds 3 and 4. The proportion of participants who lived on campus was high, 

but varied each round. Of the participants, 34% to 42% were male. Recent antibiotic use and 

recent upper respiratory symptoms were both highest during round 1, which took place during 

the winter. A high proportion of students smoked or had second-hand smoke exposure. Social 

mixing was common, as 67% to 74% of students reported visiting bars, clubs, or parties at least 

once per week. 

Also assessed were meningococcal vaccine doses received at least 2 weeks prior to specimen 

collection, to allow time to mount an immune response. A high proportion of students had 

documented MenACWY vaccine, which generally was received the summer before college 

entry. In round 1, no students had received MenB-FHbp more than 2 weeks prior. In round 2, 

most participants had received 1 dose. In round 3, most had received 2 doses. In round 4, the 

majority had received either 2 or 3 doses. 

In terms of overall meningococcal and serogroup B carriage, in round 1, 24% of participants 

were carrying Neisseria meningitidis. This proportion remained fairly stable over the next year, 

with 24% carriage in round 2, 20% carriage in round 3, and 21% carriage in round 4. When 

looking at serogroup B carriage, 4% of participants carried serogroup B by PCR in each of the 4 

rounds. By slide agglutination, just over 1% of students were carrying bacteria that express the 

serogroup B capsule in each round. 

Regarding serogroup results by PCR over time, as with previous meningococcal carriage 

studies, most isolates were non-groupable, meaning the bacteria are unencapsulated and 

therefore better adapted for colonizing the nasopharynx. Serogroup B was the most common, 

and a handful of serogroups C, Y, W, and X were detected in each round. The majority of 

isolates were non-groupable according to slide agglutination as well. With respect to the 

groupable isolates, serogroup B was the most commonly expressed capsule, though serogroup 

E increased over time and a handful of isolates expressed serogroups X, Y, C, and Z as well. 

Next, associations with carriage of any meningococcal bacteria were examined. As compared 

with round 1, there was no difference for rounds 2 or 4, but round 3 had a slight association with 

decreased carriage. In comparison to the class of 2018, who were freshmen during outbreak, 

the class of 2017 had the highest carriage prevalence. Male sex, smoking, and partying at least 

once per week were associated with increased carriage. Recent antibiotic use was associated 

with decreased carriage. Receipt of 1, 2, or 3 MenB-FHbp vaccine doses was not significantly 

associated with carriage. 

When the same models were repeated with the outcome of serogroup B carriage by PCR 

instead of any meningococcal carriage, very similar associations were observed. During the 

evaluation, only 1 individual was found to be carrying the outbreak strain. This individual 

participated only in rounds 2 and 3, and was carrying this strain during both rounds. The carried 

strain was serogroup B by PCR, but was non-groupable by slide agglutination. Whole genome 

sequencing (WGS) revealed that this was due to phase-variation in the capsule locus, meaning 

the bacteria were temporarily not expressing the capsule. It is unclear whether this change in 

expression occurred in vivo or after the specimen was collected and cultured. 

In total, 615 students participated in multiple carriage evaluation rounds. Of these students, 

71% were not carrying any meningococcal bacteria during any round; 14% were consistently 

carrying meningococcal bacteria during each round in which they participated, though not 

necessarily the same strain or serogroup; 8% were carrying meningococcal bacteria during one 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

round, but then were not carrying any meningococci during a later round; and 7% did not have 

carriage, but then acquired carriage that was detected during a later round. 

Of the 50 students who lost meningococcal carriage, 13 lost carriage after one MenB-FHbp 

dose, 32 after two doses, and 5 after three doses. Of the students, 45 acquired meningococcal 

carriage (20 after one dose, 16 after two doses, and 9 after three doses). Looking at serogroup 

B, 11 students lost serogroup B carriage (2 after one dose, 8 after two doses, and 1 after three 

doses), and 10 students acquired serogroup B carriage (3 after one dose, 4 after two doses, 

and 3 after three doses). 

In conclusion, in each round, 20% to 24% of students carried meningococcal bacteria and 4% 

specifically carried serogroup B by PCR. This overall carriage prevalence is comparable to 

previously reported prevalences of up to 34% among university students in the UK. However, 

the observed carriage prevalence was quite a bit higher than recent US estimates of 1% to 8% 

among the general population. Despite this high carriage prevalence, only 1 carrier of the 

outbreak strain was identified and no further serogroup B cases associated with the college 

have occurred. No evidence was found that MenB-FHbp vaccination impacts carriage, at either 

the population or individual level. 

These results help inform US MenB vaccine guidelines, both for use in adolescents and young 

adults, and specifically in outbreak settings. Also, if MenB vaccines do not appear to affect 

carriage and therefore provide some herd immunity, this reinforces the need for high vaccination 

coverage during outbreaks to protect each individual and emphasizes the role of 

chemoprophylaxis for close contacts. WGS is underway to further characterize the isolates, 

compare carriage versus invasive isolates, examine within-individual longitudinal data, and 

investigate MenB vaccine antigens among the carriage isolates. Additionally, concurrent 

meningococcal carriage evaluations were conducted at two other universities, and the findings 

will be compared from all 3 evaluations once they are complete. 

Immunogenicity Studies of Two MenB Vaccines in Adults 

Dan Granoff, MD, FPIDS 

Center for Immunobiology and Vaccine Development 

UCSF Benioff Children's Hospital Oakland 

Dr. Granoff noted that Men A, C, Y and W capsular based vaccines have minimal antigenic 

variability within a capsular group. For disease-causing MenB strains, protein antigens have 

large variability in amino acid sequence and expression, which can affect susceptibility to serum 

bactericidal activity. For MenB vaccine licensure, efficacy was inferred based on data against a 

limited number of reference strains. Gaps in knowledge include the extent of protection against 

more diverse disease-causing strains, as well as the effect of vaccination schedules (2 doses 

versus 3 doses), and duration of protection. 

During this session, Dr. Granoff discussed the results from three MenB immunogenicity studies 

in adults. These studies were not designed to provide comparison data between vaccines. 

Each study tested one vaccine. The studies were performed independent of industry. Dr. 

Granoff pointed out that he has no relevant potential conflicts of interest other than being the 

inventor on patents related to meningococcal vaccines. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Granoff began by sharing the conclusions so that everyone could be thinking about them 

while he described the studies. One month post-dose 2, both vaccines elicited protective 

bactericidal antibody (titers ≥1:4) against most strains. Some strains are relatively resistant to 

bactericidal activity despite prediction of susceptibility by sequence analysis and antigen 

expression. After dose 2, titers can decline within 4 to 6 months, especially for strains with low 

antigen expression. 

Study 1 was of MenB-4C (BEXSERO®) to assess immunogenicity in adults. There were two 

studies sites: Oxford Vaccine Clinic, UK (N=15) and University of California, San Francisco 

(UCSF) Benioff Children’s Hospital Oakland (N=5). The median age was 29. Of the 

participants, 12 (60%) were healthcare or laboratory workers. Participants received 2 doses on 

either a 0,1 or 0, 2 schedule. As noted earlier, MenB-4C vaccine contains four components that 

are largely responsible for bactericidal antibody: FHbp (sub-family B), NHba, NadA, and PorA 

(P1.4). A reference strain for FHbp would be considered one that was absent of NadA, PorA 

that did not have P1.4, and low expression of NHba. This would allow for inference that most of 

the bactericidal antibody was directed at FHbp. 

Regarding data on ≥4-fold increases in serum bactericidal antibody titer to MenB-4C, the titer 

one month post-dose 2 is divided by the pre-titer. So, if the subject had a titer of 16 one month 

after 2 doses and a titer of 4 before, that would be a 4-fold increase. Data from two studies 

conducted by the manufacturer for vaccine licensure that are included in the FDA package 

insert, were compared to results from Study 1 for the three reference strains. The Study 1 data 

are very comparable to the data provided in the package insert. Of the subjects, 95% to 100% 

are achieving 4-fold increases to the FHbp strain and NadA strain, and about 70% to the PorA 

strain. This is very similar to Study 2 and is higher than the manufacturer. 

In real life, there is a lot of sequence variability as illustrated by this image: 

Each of the FHbp variants can be given a different identification number (ID). The MenB-4C 

vaccine contains ID 1. The closer a variant is in the tree to the MenB-4C vaccine variant (ID 1) 

indicates the variant has a similar sequence to the vaccine variant. But they all are within the 

same FHbp family and predicted to be covered by the vaccine. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Serum bactericidal antibody responses to a number of strains were assessed that were largely 

from outbreaks of disease on college campuses in the US (UC Santa Barbara, Providence 

College, Ohio University, Santa Clara University, and Princeton University) and two strains from 

Quebec where there has been hyperendemic disease for a number of years. First, serum 

bactericidal antibody responses of healthy adults immunized with 2 doses of MenB-4C were 

presented for FHbp sub-family B containing strains. Dr. Granoff noted that the strains also had 

other antigens in the vaccine present. Although all strains had at least 2 antigens and some 

had 3, the 4-fold increases were very similar to the reference strain, which had an FHbp that 

was an exact match with ID 1 that is contained in the MenB-4C vaccine. The 4-fold increases 

were much lower with strains that had other FHbp variants [Giuntini et al, Clin Vac Immunol 

2016, in press]. Dr. Granoff emphasized that a 4-fold response is a measure of a robust 

response; however, it does not indicate whether the individual is protected. He indicated that he 

would show some data from the Quebec strain where there was 35% 4-fold rise, and most of 

the persons at 1 month post-dose 2 actually had protective titers. So, there are really two 

different measures. His working model is that the portion with 1:4 or greater is a good measure 

of short-term protection; whereas, the 4-fold response gives a sense of the magnitude of the 

response and is likely to correlate with duration of protection. Again, this is a model. 

In terms of the data for the same sera looking at a group of strains from FHbp sub-family A, the 

FHbp was mismatched and depended on the other antigens in the MenB-4C vaccine (NHba and 

NadA). The serum bactericidal antibody responses of adults immunized with 2 doses of MenB4C were pretty uniform, even for the strain that was mismatched for all 4 antigens, with around 

30% to 40% 4-fold increases in bactericidal titer. 

Study 2 was of MenB-FHbp (Trumenba®) to assess immunogenicity in adults. There were two 

study sites: UCSF Benioff Children’s Hospital Oakland (N=12) and University of Massachusetts 

Medical Center (N=5). The median age was 40. Of the subjects, 100% (N=17) were healthcare 

or laboratory workers. Three doses were used at the recommended schedule (0, 2, 6). There 

are two FHbp antigens in this vaccine, sub-family A and B. The Pfizer nomenclature is BO1, 

which is ID 55 and AO5 for the sub-family A, which is ID 45. There is a relationship to a number 

of the other variants, which were contained in the strains that were tested. 

In terms of the serum bactericidal antibody responses of adults immunized with MenB-FHbp on 

a 2-dose (0,2) schedule, for many of the sub-family A strains more than 70% of subjects had ≥4­

fold increases in hSBA titers [Lujan et al, IPNC 2016]. With the MenB-4C vaccine, 40% of 

subjects had ≥4-fold increases in hSBA titers for sub-family A strains. Dr. Granoff noted that 

they do not actually have the Pfizer reference strains in their laboratory to test, and that he was 

showing the data from the package insert. He has found similar responses for the 2 doses of 

this vaccine to the two sub-family A strains that were used by Pfizer. 

With MenB-FHbp, a third dose is given at 6 months. In terms of the data showing the 4-fold 

responses after 2 doses and 3 doses, the 3-dose data is one month post-dose 3 compared to 

the pre-titer. With the third dose, there was a significant increase for many of the subjects and 

strains, with most having 80% to 90% 4-fold increases [Lujan et al, IPNC 2016]. Again, Dr. 

Granoff’s data are similar to what were reported for sub-family A. 

For sub-family B, Dr. Granoff showed data for 2 doses at the 0, 2 schedule. There was quite a 

lot of variability. A mutant strain, H4476, was included. This is a low expressing mutant, with 

about 50% lower expression than in a wild type. Having lower expression affects the ability of 

the antibodies elicited by the vaccine to result in a robust bactericidal response. The results 

with the two doses of MenB-FHbp vaccine administered at 0,2 months were within in the same 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

range as the MenB-4C vaccine. The Pfizer data were very similar to what were reported for the 

sub-family B strains. Giving a third dose of MenB-FHbp vaccine at 6 months results in 

significant increases for many of the strains, with almost all being over 70% 4-fold [Lujan et al, 

IPNC 2016]. Again, the data are quite similar to what was reported. 

Turning to comparative bactericidal titers for a representative strain from Quebec, Dr. Granoff 

pointed out that persons who are likely to benefit most from vaccination are those who have 

titers of <1:4 before vaccination with MenB-4C. Out of a group of 20 subjects, 14 had titers <4. 

Although most of them did not achieve 4-fold response, 11 of 13 had protective titers after dose 

2. A small number of subjects had samples obtained 4 months post-dose 2, and they tended to 

decline. Individuals with low titers tend to decline to below 1:4. The results were very similar for 

MenB-FHbp. After 2 doses, 13 of 16 had titers of 1:4 or greater and then there was a decline in 

titers. After a third dose of MenB-FHbp, 11 of 12 subjects had a boost in protective titers. 

There are no follow-up sera on these at this point [Quebec 2013, Hyperendemic]. 

Study 3 assessed immunogenicity among students from Santa Clara University who received 

MenB-4C. Between January 31 through February 3, 2016, there were 3 cases (2 cultureconfirmed and 1 suspect) at Santa Clara University caused by a strain that was in the ST 32 

clonal complex. Within a few days, MenB-4C vaccination clinics were organized at the 

university. From February 4-8, the first dose of vaccine was administered to 4921 persons. The 

vaccine was administered on March 18 and April 6-8 to 4731 persons, most of whom were 

receiving a second dose. Sera were collected May 23-25 from 246 students (0 dose, N=52; 1 

dose, N=91; and 2 doses, N=101). 

Serum bactericidal was measured against the three college outbreak strains from Santa Clara, 

Princeton, and Ohio Universities. Santa Clara University students were immunized with MenB4C; that strain was positive for three MenB-4C antigens: FHbp subfamily B (ID 510), NadA, and 

NHba. Protective titers of ≥1:4 were 92% post-dose 2 and 66% post-dose 1. Interestingly 

against this strain, about 40% already had protective titers before vaccination and 20% had high 

titers [Interim analysis of results on 160 sera by Dr. Qin Liu, Wistar Institute, Philadelphia]. 

The investigators also evaluated the strain causing the outbreak at Princeton University where 

there were 9 cases and 1 death. This strain expressed two MenB-4C antigens: FHbp subfamily 

B and NHba. A previous study showed that 66% of the students immunized with 2 doses of 

MenB-4C had developed protective serum bactericidal titers ≥1:4 [Basta et al, NEJM 2016]. 

Looking at the Santa Clara University sera against the Princeton strain, the prevalence of 

background antibody was much lower with almost nobody having a titer of ≥1:16. There was a 

significant increase in serum bactericidal activity after 1 dose. After 2 doses, 69% had titers of 

1:4 or greater. So the investigators actually replicated the data from Basta at Princeton 

University, indicating that the strain is relatively resistant, especially when compared to the 92% 

protective titers against the Santa Clara University strain. 

Finally, they looked at an outbreak strain from Ohio University where there had been 13 cases 

and 1 death for the outbreak strain that expressed of three MenB-4C antigens: FHbp subfamily 

B (ID 15), NadA, and NHba. Looking at the data again from the interim results, the background 

level of antibody was very low in the Santa Clara students against this strain. After 2 doses, 

approximately 52% had titers of 1:4 or greater and about 10% had titers of greater than 1:16 

despite the fact that there was a match in the antigen and expression of MenB-4C FHbp, NadA, 

and NHba. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

To conclude about these vaccines, first of all, they are complex. At least 4 antigens are capable 

of eliciting serum bactericidal activity. The antigen-specific reference strains that were used for 

licensure are more susceptible to vaccine-induced bactericidal antibodies than many circulating 

disease-causing strains. Some strains are relatively resistant to bactericidal activity despite 

prediction of susceptibility by sequence analysis and antigen expression, such as the Princeton 

University and Ohio University strains. The great majority of subjects have titers of ≥1:4 at 1 

month post-dose 2 against most strains. Titers decline by 4 to 6 months, especially against low 

FHbp-expressing strains. 

For the MenB-FHbp, Dr. Granoff said he thought the 2-injection data were the most interesting 

because they basically saw very similar or higher ≥4-fold increases in serum bactericidal activity 

as MenB-4C at 1 month post-dose 2. The great majority of subjects, had titers of ≥1:4 at 1 

month post-dose 2 against most strains. Titers decline by 4 months, especially against low 

FHbp-expressing strains. The recommended third dose of MenB-FHbp at 6 months boosted 

titers. Additional data on antibody persistence are needed, which should include strains 

relatively resistant to vaccine-induced bactericidal activity to get a sense of the variability on 

antibody persistence. 

In terms of the limitations, these were independent studies that were not designed to provide 

comparison data between vaccines, and the populations are different. There are relatively few 

sera 4 to 6 months post-dose 2. That was added at the end of the protocol and it was not 

possible to get everybody. The serum bactericidal assays used research assays and were not 

the type that would be FDA-validated, although the assays are robust. The data on the Santa 

Clara University study are on antibody prevalence. They do not have pre-vaccination sera, but 

it is possible to compare the 0 dose to the 1 doses and 2 doses. Dr. Granoff emphasized that 

this is an interim analysis that requires much more work. 

Discussion Points 

Rino Rappuoli (GSK) commented that it is important to keep in mind that Bexsero® has 4 

different components targeting completely different antigens, and each of them can kill the same 

bacteria. He noticed that in the Trumenba® between 2 and 3 doses, there was a pretty good 

increase in immunogenicity and coverage. That is more or less what has been observed with 

Bexsero® between 1 and 2 doses. Bexsero® was licensed as a 2-dose vaccine after multiple 

studies. In one case during the Phase 3 trials, they also did 3 doses and did not see that kind of 

increase. So, it looks like Bexsero® increases between 1 and 2 and Trumenba® increases 

between 2 and 3 doses. Also important to remember is that while the 4-fold increase is a way to 

look at the longevity of protection, that may underestimate the number of protected people 

because many people may have a protective titer above 1:4 by bacterial assay and still not have 

a 4-fold increase. Obviously, all of the serological findings are important, but they are always a 

surrogate for real data in the field. That is what has been missing during the development of 

vaccines for so long. In the case of Bexsero®, there are two types of data. One comes from 

multiple uses in outbreaks in the US and Canada where 2 doses have been used in many 

instances. There have not been breakthrough cases, which is very important to remember. 

Second, are the data from the UK where Bexsero® is being used in infants to vaccinate all of the 

newborns beginning September 2015. Two doses were used in infants. Infants are completely 

naïve to meningococcus, so they are more difficult to protect than adolescents. With 2 doses, 

Public Health England (PHE) reported effectiveness of 83% a month ago in a meeting in 

Manchester. Basically with Bexsero®, there is extremely high effectiveness in the field in a very 

difficult population. 

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Dr. Friedland (GSK) congratulated the Rhode Island meningococcal carriage group for 

undertaking such an important study. Certainly, the evaluation of the impact of the 

meningococcal B vaccines Trumenba® and Bexsero® on carriage is very important. GSK is 

committed to continue to evaluate the impact of Bexsero® on carriage, and is in the final stages 

of finalizing the protocol to evaluate the impact of Bexsero® on carriage in over 30,000 

individuals that will be powered to detect even small differences in carriage. GSK thinks this is 

very important, and looks forward to sharing these data with ACIP as they become available. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Walter said he noticed from Dr. Soeters’ presentation that the coverage for vaccination 

declined from 94% for the first dose to about 80% to 77% for the second and third doses 

respectively in the campaign. He asked whether there was any sense for why that was, in 

terms of whether it was that people were concerned at the start of the campaign about disease, 

or if it was due to concern about side effects. 

Dr. Soeters responded that overall, a drop-off has been observed in MenB vaccine campaigns 

at a lot of the colleges that have had outbreaks. In this particular case, the school did 

something unusual, which was that they required all students to come to the vaccination clinics 

and they could sign declination forms that they did not want a vaccine. That is how they 

achieved high coverage during the first round. They did continue to require it, but students 

seem to have caught on that if they did not appear, nothing happened to them. A lot of the 

students experienced and mentioned sore arms, but she did not hear students saying that that 

was a reason they did not return for vaccination. Other surveys are being conducted to gather 

more information about students’ opinions about the vaccine and what was influencing their 

decision to get vaccinated or not. 

Dr. Belongia requested clarification about the titer of 1:4 as a protective titer and the basis for 

using that as a correlate of protection. 

Dr. Granoff responded that it went back to a Goldschneider study in the 1960s published in the 

Journal of Experimental Medicine (JEM) in which they looked at military recruits. They collected 

serum samples at the time recruits began training. There was a serogroup C outbreak, and 

quite a few cases occurred over the next few months. Then they retrospectively collected sera 

from the people who got disease and had a sample of about 500 sera for people who did not get 

disease. A titer of 1:4 or greater essentially offered about 90% to 95% protection against 

developing serogroup C disease. Almost all of the cases were among people who lacked titers. 

There also was a carriage study going on, and they detected about 30 carriers. About a third of 

those actually went on to get disease. This was serogroup C, and this was natural antibody. It 

was not vaccine. Having a titer of 1:4 really correlated with protection. Suffice it to say that 

collectively, the data are pretty convincing that a titer of 1:4 does predict protection. A titer of 

less than 4 does not necessarily mean that someone is susceptible, but was associated with all 

of those cases. This has been accepted by regulatory authorities all over the world, including 

the FDA as the basis of licensure. These vaccines were not tested in efficacy studies. They 

used the 1:4 and the 4-fold composite to look at the immune responses, and that was the basis 

of deciding vaccination schedules and inferring efficacy for the vaccine. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Paradiso (Paradiso Biologics Consulting) pointed out that when looking at bacterial carriage 

in the nasopharynx, it is generally considered that clearing bacteria is totally different than 

affecting acquisition of new bacteria. Often in carriage studies, it is looking at blocking the 

acquisition of new bacteria. He noted that those were separated out in the carriage study, but 

the numbers were very small. Of these subjects aged through 20 years of age, 20% or more 

had carriage that they had gained somewhere along the way probably based on the 

epidemiology when they were 14, 15, or 16 years old. He wondered whether there was an 

opportunity or a plan to back up in the age group to see if acquisition could be stopped in a 

younger age group before it builds up to the 15 or 16 year olds, or if that is even feasible to do. 

He also thought it was interesting that these two vaccines are not really group-specific 

completely, because they are protein antigens. For all of the strains for which a group could not 

be assigned, there was little impact. 

Dr. Soeters replied that there are no current plans to look at carriage in adolescents, but they 

are beginning to examine the within-individual dynamics in carriage over time in this particular 

population to determine if they are carrying the same strain or if it changes. It seems like some 

of the students can carry for a couple weeks, while some can carry for a couple of months. It is 

not clear whether they are acquiring some of these strains in adolescence and then bringing 

them to college with them, or if there is just a lot of circulation and transient carriage occurring. 

Incoming freshman entering campus the year after the outbreak were seen their first week on 

campus and then again 6 months later, and an increase in carriage was seen in those incoming 

freshman. 

Dr. Maldenado (AAP) asked whether there was a possibility of comparing current data to the 

nicely done natural history colonization studies from the 1950s looking at some of the Army 

studies done in California and other places in terms of baseline colonization and what happened 

and the impact of antibiotic prophylaxis and resistance. Obviously, there are better genetic data 

now. There seem to be many parallels in terms of what happens to these people and, more 

importantly, if someone is known to be carrying, what should be done with that patient. What 

was shown in the Army studies was that it did not have a huge impact if there was a lot of 

rifampin resistance. 

Dr. Soeters replied that while this has not been done, it can be. 

Dr. Messonnier added that there is a variety of literature on this, including studies that Dr. 

Stephens and she tried to conduct in adolescents and high school students 10 years ago, 

getting really low carriage. This is a complicated field, and CDC is very much looking forward to 

the data from pharmaceutical companies with much higher enrollment rates. The prospective 

studies CDC has tried to conduct have had sample size power problems. When they have tried 

to do it in convenience around outbreaks, there have been numerous problems. The large 

study being planned may help. 

Dr. Stephens added that one of the issues is that there is now a lot better typing systems and 

understanding very specifically, for example, in the study only one individual was carrying the 

outbreak strain. That is quite a difference from what was known in the old military studies. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

MenB-FHbp (Trumenba®) Vaccine Update 

Dr. Laura York 

Medical Development 

Scientific and Clinical Affairs 

Pfizer 

Dr. York presented an update on Trumenba®, which was licensed in October 2014 and received 

FDA approval through the accelerated approval regulations to be used in a 3-dose series of 0, 

2, and 6 months for prevention of meningococcal B disease in individuals 10 through 25 years 

of age. This was in response to the unmet need with the outbreaks occurring in the US. Pfizer 

continued to discuss the schedules with the FDA, and the FDA approved a label change under 

the same regulations on April 14, 2016. The schedules now include a flexible 3-dose schedule 

(0, 1-2 months and 6 months) and a 2-dose schedule (0, 6 months). Both schedules were 

determined by the FDA to be safe and effective. With the two different schedules in the 

labeling, ACIP guidance is needed in reference to the existing recommendations for providers 

as they move forward with use of these vaccines. Dr. York briefly reviewed the data that 

supported the change in the label, and provided some new data on persistence and immune 

responses following a booster in terms of both schedules. 

Pfizer’s MenB vaccine, Trumenba®, is based on a surface-exposed factor H binding protein 

(FHbp), which functions as an important immune evasion mechanism. It actually downregulates 

the complement cascade and limits the bactericidal activity of complement in that membrane 

attack system. This protein is expressed in over 97% of the invasive MenB strains that Pfizer 

has examined, and there has been a comprehensive evaluation survey of invasive 

meningococcal isolates from 2000 on from the US, several countries in Europe, and Canada. 

The FHbp sequences segregate into two genetically and immunologically distinct subfamilies 

referred to as A and B. Trumenba® is composed of two lipidated proteins, A05 and B01, one 

from each subfamily. The lipidation of that protein is important and really contributes to the 

breadth of protection observed in terms of the ability to elicit antibodies that could recognize 

across the diversity of this particular antigen; that is, recognizing across that subfamily and the 

variance within that subfamily. The vaccine-elicited protective responses are actually 

demonstrated not through efficacy studies because of the disease incidence of meningococcal, 

but through the correlate used to predict protection which is the serum bactericidal assay using 

human complement (hSBA). Pfizer uses 4 invasive MenB strains that are representative of 

prevalent strains in the US and Europe. The 4 strains express fHBP variants that are different 

from what is in Pfizer’s vaccine (A22, A56, B24, B44). The approach was designed to 

demonstrate the breadth of coverage. Where those 4 strains are representative, they would be 

expected to predict the activity against other strains. 

The data that contributed to being able to have two schedules and the change in the dosing and 

administration was from a study (B1971012) that was done in Europe that included individuals 

11 through 18 years of age who were randomized into 5 groups to examine two 3-dose 

schedules and three 2-dose schedules. The participants were enrolled into an additional study, 

or a follow-on study, with a different number (B1971033) to evaluate the antibody persistence 

annually and the response to a booster dose at approximately 4 years. The choice of that 

timing was not to determine when to give a booster dose, but to look at the ability to boost the 

response—to look for memory. Pfizer knew that these data would be important to ACIP in their 

considerations of use of the vaccine, so the timing for Pfizer to have these data was based on 

being able to provide additional information for ACIP’s consideration. 

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The immune response was evaluated on the 4 representative strains, and the proportion of 

individuals who have a 4-fold response are assessed. As Dr. Granoff said, this is really looking 

at the vaccine response and the robustness of the response. The minimum titer that a person 

has to achieve is 1:16 to be recognized as a responder with a 4-fold response. A composite 

response also was assessed, which is looking at the ability of the antibody generated in an 

individual to recognize each of the 4 strains all together. This shows the ability of the antibody 

to recognize across a diversity of the antigens. Dr. York reminded everyone that she had 

already shown data on 10 additional strains to highlight how these data demonstrate the 

immune response that is elicited by Trumenba®. 

Looking at the immune response in terms of 2-dose schedules at different intervals (0,1 / 0,2 / 

0,4 / 0, 6), 0,1 comes from the 3-dose schedule looking post-dose 2 on a 0, 1, 6 interval. In 

terms of 4-fold and the composite response, as the interval between vaccine doses is 

increased, there is an improvement on the immune response acquired from receiving the 

vaccine. This is very important in terms of the 0,6 interval providing robust responses and 

substantial protective responses in terms of the 4-fold response, and also in terms of composite 

response with a point estimate of 73.5%. This is a nice, robust, substantial protective immune 

response with a 2-dose interval that is 6 months. 

In terms of 3-dose schedules, there are circumstances in which it is desirable to give 2 doses in 

close interval. In an outbreak, for example, the goal is to achieve an immune response as 

quickly as possible in as high a number of individuals as possible. It is known from the 3-dose 

schedule that a 0,1 or 0, 2 schedule can be used to quickly achieve a comparable type of 

response. But, in fact, there is an improvement in terms of the percent of responders observed 

with the third dose in the 3-dose schedules. Dr. Granoff’s data show very clearly in terms of a 

2-dose schedule at 0,2 or 0,1 that there is a very effective immune response. But, in order to 

have a high proportion of individuals who are going to respond and have a broadly protective 

response, the third dose will provide it in the 3-dose series. 

This trend also is observed when looking at the response in terms of the percent of subjects 

who have an hSBA titer of greater than 1:8 and 1:16 on one of Pfizer’s test strains. Again, this 

is higher than the protective correlate of 1:4 that is accepted from the studies conducted very 

early in the military in terms of the effect of that interval, the range of response anticipated to 

provide a short interval versus a longer interval of a 2-dose series, and the 3-dose series also 

giving a robust response, a high percentage of individuals, and a high range of response that 

would be predicted to be seen against other diverse strains. This also is seen in the GMT with 

the 6-month interval resulting in slightly higher responses in terms of GMT that are, in fact, more 

comparable to the 3-dose series. For some of these responses in terms of the percent of 

individuals with a titer greater than 1:8 or on the GMT that there are overlapping confidence 

intervals, the two schedules are expected to be effective, and that is why Pfizer has these two 

schedules in its label. There is no differentiation in terms of safety between the second or the 

third dose, so consequently there was FDA approval in terms of safety and efficacy of this 

vaccine on a 2-dose schedule at 0,6 or a 3-dose schedule of 0, 1-2, or 6 months. 

Regarding the persistence data following either a 0,6 or 0, 2, 6 schedule of Trumenba® in terms 

of the percent of subjects with an hSBA titer of greater than 1:4 among two cohorts against the 

4 representative strains. As found in a previous study and presented to ACIP, a plateau is 

established after a waning of the persistence in terms of the percent responders. There seems 

to be a consistent plateau over the 48 months for Trumenba®. There is a divergence with two of 

the strains, but the confidence intervals do overlap, which suggests that the response after a 2­

dose schedule or a 3-dose schedule will provide persistence in terms of the protective 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

response. There is a lowering of the response in terms of the percent or the range observed 

against diverse strains, but clearly in terms of the population, there still is a protective response 

against MenB. 

It was interesting for Pfizer to look at the hSBA responses following a booster about 4 years out 

of individuals having either a 2-dose schedule at 0,6 or a 3-dose primary schedule at 0,2,6. For 

simplicity, Dr. York showed a graphic reflecting the response in terms of the pre- and postprimary series and then 48 months post-primary series. 

These are the data shown previously but without all of the additional time points from 12 months 

through to 48 to make a point in terms of the booster response that is observed against these 4 

representative strains showing a significant percentage of individuals who are responding to a 

single booster dose. The composite of this is now well over 90%. Clearly, there has been 

induction of memory at approximately the same level of memory with either a primary series of 

the 0,6 or a primary series of 0,2,6. 

The memory response is also well-defined in terms of the hSBA GMT responses to the booster 

dose, with significant responses shown in terms of GMT after a primary series of the 2-dose or 

the 3-dose schedule, maintaining the plateau in terms of the persistence above the protective 

level of 1:4. There is a significant increase in the GMT post-booster, which demonstrates the 

memory response. Regarding the safety of a booster dose, a difference is not observed in 

terms of the safety profile. Therefore, there is nothing untoward in terms of receiving a booster 

for approximately 4 years post-primary series. 

In summary, Trumenba® (MenB-FHbp) was granted FDA approval under Accelerated Approval 

regulations in April 2016 resulting in a flexible schedule for use in a 3-dose series at 0,2,6 

months or a 2-dose schedule at 0,6. Either schedule can be used to provide protection against 

invasive meningococcal disease caused by serogroup B in individuals 10 years through 25 

years. These data demonstrate that both schedules provide a significant benefit in terms of the 

breadth of coverage against the diverse MenB strains causing disease. There is flexibility within 

the 3-dose schedule that may be beneficial when an individual is at significant risk of disease 

(e.g., outbreak). A 2-dose schedule may improve compliance in an age group where 

completion of a multi-dose series is challenging. Based on the data, there is similar persistence 

of the hSBA response. Clearly, after either series the immunological memory is established and 

a booster dose elicits a response that is actually higher than the response after the primary 

series. 

Discussion Points 

In terms of receiving the FDA labeling and both schedules were determined to be safe and 

effective, Dr. Lee asked at what time point the effectiveness was assessed. In addition, she 

asked whether there were any long-term follow-up studies that go beyond what Dr. York 

showed. 

Dr. York replied that it was always one month after the primary series. All of the vaccines are 

licensed on that. No long-term follow-up studies are planned. However, there will be another 

blood draw after the booster dose, so they will be able to present data to ACIP about a year out 

from that booster dose. This will show whether the waning is less and plateauing within that. 

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Ms. MacNeil presented a summary of the WG’s considerations for the use of 2- and 3-dose 

schedules of MenB-FHbp or Trumenba®. As a reminder, there are two serogroup B MenB 

vaccines licensed for use in the US in persons 10 through 25 years of age. MenB-FHbp 

(Trumenba®) contains two components (fHbp subfamily A/v2,3; subfamily B/v1) and originally 

was licensed by the FDA in October 2014 for administration as a 3-dose series. MenB-4C 

(Bexsero®) contains four components (fHbp subfamily B/v1; NhbA; NadA; Por A1.4) and was 

licensed by FDA in January 2015 for administration as a 2-dose series. MenB-4C also is 

licensed in a number of other countries for use in persons 2 months of age and older. 

 

 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Considerations for Use of 2- and 3-Dose Schedules of MenB-FHbp 

Jessica MacNeil, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Current ACIP Recommendations for the use of serogroup B MenB vaccines are: 

Certain persons aged ≥10 years who are at increased risk for meningococcal disease 

should receive MenB vaccine (Category A)1 

A MenB vaccine series may be administered to adolescents and young adults aged 16– 

23 years to provide short-term protection against most strains of serogroup B 

meningococcal disease (Category B)2 

In both of the MenB Policy Notes, the following additional guidance is provided that is consistent 

with the original licensure: 

MenB vaccine should either be administered as a 3-dose series of MenB-FHbp 

(Trumenba®) or a 2-dose series of MenB-4C (Bexsero®)1,2
 

[

1Folaranmi T., et al. Use of Serogroup B Meningococcal Vaccines in Persons Aged ≥10 Years 

at Increased Risk for Serogroup B Meningococcal Disease: Recommendations of the Advisory 

Committee on Immunization Practices, 2015. MMWR; June 12, 2015; Vol. 64, No. 22, p 608­

612; 2MacNeil JR, et al. Use of Serogroup B Meningococcal Vaccines in Adolescents and 

Young Adults: Recommendations of the Advisory Committee on Immunization Practices, 2014. 

MMWR; October 23, 2015, Vol. 64, No. 41, p 1171-1176]. 

The FDA approved updates on April 14, 2016 to the dosage and administration section for 

MenB-FHbp. The original and updated language follows, with the changes underlined: 

Original Language: 

 Three doses according to a 0, 2, and 6 month schedule 

Updated Language: 

 Three-dose schedule: Administer a dose at 0, 1-2, and 6 months 

 Two-dose schedule: Administer a dose at 0 and 6 months 

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

 A MenB vaccine series may be administered to adolescents and young adults aged 16– 

23 years to provide short-term protection against most strains of serogroup B 

meningococcal disease (Category B) 

However, because of the recent change in licensure for MenB-FHbp during the remainder of 

this discussion, the focus was specifically on MenB-FHbp in order to provide guidance from 

ACIP on when the 2- and 3-dose schedules of MenB-FHbp (Trumenba®) should be used. After 

reviewing the data, the WG discussed several different policy options. First, for persons at 

increased risk and for use during outbreaks, a preference for 3-dose schedule of MenB-FHbp 

was proposed. For healthy adolescents, three possible policy options were proposed: 1) A 

preference for 2-dose schedule (0, 6 months); 2) An option for either the 2- (0, 6 months) or 3­

dose (0, 1-2, 6 months) schedule; or 3) A preference for 3-dose schedule (0, 1-2, 6 months). 

Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

The choice and dosing schedule may depend on the risk of exposure and the patient’s 

susceptibility to meningococcal serogroup B disease 

Ms. MacNeil discussed the WG’s interpretation of the MenB-FHbp data pertaining to short-term 

immunogenicity, antibody persistence, safety, the proposed policy options for 2- and 3-dose 

schedules of MenB-FHbp, and the WG’s discussions. As a reminder, several dosing schedules 

were evaluated for MenB-FHbp, including two 3-dose schedules and four 2-dose schedules. 

For this presentation, Ms. MacNeil focused on the data presented for the 2-dose schedule at 0,6 

months and two 3-dose schedules. 

Regarding the short-term immunogenicity data one month following the last dose, among the 2­

dose schedules evaluated, the 0, 6 month schedule had the highest proportion of responders 

and GMTs and is most similar to a 3-dose schedule. However, the proportion of subjects 

demonstrating a composite response to all four primary strains is slightly lower with a 2-dose 

schedule at 0, 6 months compared to either 3-dose schedule. Similarly, for most strains, the 

GMTs are lower with a 2-dose schedule at 0, 6 months compared to either 3-dose schedule. 

For some strains, the 95% confidence interval around the GMTs do not overlap. 

Antibody persistence to the four primary strains is shown here for participants who received 2 

doses at 0,6 months or 3 doses at 0,2,6 months. The percent of subjects with hSBA titers ≥1:4 

to the four primary strains is similar through 48 months for adolescents who received either 2 or 

3 doses of MenB-FHbp. 

In addition, the GMT responses to a single booster dose 4 years following the receipt of either 2 

or 3 doses of MenB-FHbp are similar. As has been presented to ACIP previously, the MenB 

vaccines are more reactogenic than other vaccines given during adolescence. The most 

common AE reported is pain at injection site. Overall, the safety and tolerability profiles are 

similar for the 2-dose and 3-dose schedules of MenB-FHbp. 

Again, there are two MenB vaccines in the US for persons aged 10 through 25 years of age: 

MenB-FHbp (Trumenba®, Pfizer) and MenB-4C (Bexsero®, GlaxoSmithKline). ACIP does not 

express a preference for either vaccine product. The current ACIP recommendations for the 

use of serogroup B meningococcal vaccines are show here as a reminder, with no changes 

proposed during this session: 

Certain persons aged ≥10 years who are at increased risk for meningococcal disease 

should receive MenB vaccine (Category A) 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Based on the discussions of the WG, there was agreement that ACIP guidance for which 

schedule to use in each population is needed. There was strong consensus in the WG to 

express a preference for the 3-dose schedule for persons at increased risk, including during 

outbreaks, to provide early protection and to maximize immune response. For healthy 

adolescents, the WG’s considerations included the following: 

Preference for 2-dose schedule OR option for 2- and 3­

dose schedules the key considerations were as follows: 

Persistence of the hSBA responses for the 2-dose 

(0, 6 m) schedule is similar to the 3-dose (0, 2, 6 

m) schedule 

hSBA GMT responses following a booster dose are 

also similar for 2-dose. 

However, the WG noted that providing an option 

for either the 2- or 3- dose schedule does not 

provide explicit guidance to the physician on which 

schedule to use in healthy adolescents 

When considering a preference for the 3-dose 

schedule, the key considerations were as follows: 

For people who want to maximize short- term 

protection, 3 doses is preferred 

Both the 2- and 3-dose schedules take 6 months to 

complete 

ACIP could provide guidance that if someone 

receives their second dose of MenB-FHbp 6 

months or more after the first dose, no additional 

doses would be needed 

Based on these considerations, the strong consensus of the WG was to express a preference 

for 2- and 3-dose schedules as follows: 

1.	 For persons at increased risk for meningococcal disease and for use during serogroup B 

outbreaks, 3 doses of MenB-FHbp should be administered at 0, 1-2, 6 months 

2.	 When given to healthy adolescents who are not at increased risk for meningococcal 

disease, 2 doses of MenB-FHbp should be administered at 0 and 6 months 

Discussion Points 

Dr. Walter asked whether the WG discussed harmonization of the schedule to 0,6 months for 

both vaccines when given to healthy adolescents. 

Dr. MacNeil responded that the WG did not discuss that. 

Dr. Atmar pointed out that the data shown reflected clear differences at 7 months, but in terms 

of the early protection, he wondered whether there were data about immunogenicity or serum 

antibody levels at earlier time points. That is, other than the benefit at 7 months, what is the 

benefit of receiving an extra dose at 1 to 2 months or 2 to 3 months compared to not getting that 

dose. 

Ms. MacNeil replied that the data show that the longer the interval between the doses, the better 

the response is. 

Dr. Atmar clarified that his question pertained to the early protection implying that within several 

months as opposed to at the 7-month time point, there were clear-cut differences. Usually in 

these studies, blood is drawn in each vaccination time point. He wondered whether this 

information was available to the WG and, if so, just was not presented to ACIP. 

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Dr. Cohn clarified that with the 0,6 schedule, data show that there is a similar response after the 

second dose. If doing the 0, 1-2, 6 schedule, there will be some protection earlier than if using 

the 0, 6 schedule. That is why the preference was for people at increased risk or at an 

immediate risk to use the 3-dose schedule. 

Dr. Maldonado (AAP) asked whether consideration was given to the scenario of a fully 

vaccinated high-risk person who is past the point of antibody titers dropping off being placed in 

a high-risk situation. 

Ms. MacNeil replied that the next topic the WG will discuss is boosters for people at increased 

risk, and whether someone would need to be re-boosted if placed at increased risk. 

Dr. Zucker (New York City Department of Health and Mental Hygiene (DOHMH)) pointed out 

that from a programmatic point of view, for registries this will mean that they will schedule the 

MenB series at 0, 6. There is a challenge translating the ACIP guidance into what registries will 

tell providers to do. Most often, providers will listen to the registry and they may not think about 

whether someone is at increased risk. As long as that is the intent, that is fine. They could 

translate that into guidance for the pediatric community. 

Dr. Moore recalled that Dr. Hunter had mentioned whether immunization registries could key the 

forecasting based off of the brand of initial vaccine given, so that it would be keyed at a different 

interval if it were Bexsero® given first versus Trumenba® given first. She wondered whether Dr. 

Zucker could speak to this issue. 

Dr. Zucker (New York City Department of Health and Mental Hygiene (DOHMH)) replied that 

most registries can do this, but it depends upon whether they receive a lot number and whether 

it has been reported as a particular product. It could come in as a MenB such that the product 

is not specified for them. 

Dr. Moore emphasized that this created its own complications, because this is one vaccine for 

which the brands are not supposed to be mixed. That is, 2 or 3 doses should be given of the 

same brand of vaccine. 

Dr. Lee asked whether data would be presented at the next meeting about Bexsero® and 0,6 

versus 0,1. She agreed with Dr. Walter that this can be done in an incremental way, but it 

would be helpful to know where they are headed in the long-term. Otherwise, it will not be 

practical to implement this from a programmatic standpoint. 

Dr. Friedland (GSK) indicated that the 3-dose data have been reviewed by the FDA and the 

ACIP WG in the past. The vast majority of all of the clinical trials with Bexsero® were with 2 

doses, and 2 doses were examined on different schedules: 1 month after, 2 months after, or 6 

months after the first dose. In this situation, the percentage of subjects who achieved the 

protective titer of 1:4 was high regardless of the schedule. That is, a very high proportion of 

subjects achieved seroprotection on the 0,1 schedule and there was no increase in the 

percentage of subjects getting a seroprotective level when given 6 months later versus 1 month 

later. This was the rationale for the indication that the second dose of Bexsero® can be given as 

soon as 1 month after the first dose. 

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Dr. Lee requested that this be considered more broadly in terms of thinking about whether 

someone at high risk could receive a 0,1 or 0,1,6 schedule and if doing this for a permissive 

routine recommendation, that they just do 0,6. From a clinical standpoint, it will be easier not to 

have confusing recommendations. 

Ms. MacNeil replied that the WG certainly can discuss this. 

Dr. Friedland (GSK) said that when they speak to healthcare providers about the use of 

Bexsero® in clinical practice, they hear that the flexibility of giving the second dose as soon as 1 

month after the first dose can be very important. For example, if a student presents to their 

practice during the summer months, the family can complete the full series of both doses over 

the summer before they go to college. They are hearing that having flexibility is quite important 

to and valued by healthcare providers. 

Dr. Middleman (SAHM) asked for clarity regarding the statement “for persons at increased risk 

and for use during outbreaks” preference for a 3-dose schedule meant that the WG had a 

preference to only recommend the 3-dose schedule or that the WG would allow for either one, 

but a preference for the 3-doses. She would like to be able to still have the option for those 

healthy adolescents who want 3 doses to be able to get 3 doses and not be limited to 2 doses. 

Ms. MacNeil clarified that the intent is for people who are at increased risk or during outbreaks 

to receive 3 doses so that they would have the early protection. 

Dr. Messonnier clarified that the WG does not make recommendations and was just expressing 

their preferences for ACIP to make recommendations. The vaccine licensure allows for clinician 

flexibility. CDC has received feedback that it is already incredibly confusing to have the A 

versus B recommendation and the two different vaccines. There is a value placed on ACIP 

trying to make a recommendation that is as simple as possible in this area in a space that is 

already very complicated. 

Dr. Stephens added that the WG spent a lot of time on this question and trying to wrestle with 

the question in terms of whether they preferred a specific 0,6 or an option. They came to the 

conclusion that it would create more confusion with a mixed signal in terms of being able to do 

either one. In the view of the majority of the WG, the data would support the 0,6 schedule for 

healthy adolescents not at risk in a routine administration setting. 

Dr. Kempe emphasized that insurance companies will or will not cover 3 doses for healthy 

adolescents, which is an implementation issue. She asked whether this was the ACIP saying 

that either is okay, but they have a preference for one. It did not sound like the objective was to 

make a recommendation for one. 

Dr. Messonnier reminded everyone that there are two places in which decisions are made about 

coverage. One of them is a VFC vote, which ACIP has the power to make. However, the VFC 

vote’s purpose is separate from the ACIP recommendation because it is meant to be a second 

step. Then there is the ACA, which is set up to be driven by what is on the immunization 

schedule. That is different, separate, and a discussion that would occur the next day during the 

schedule session. It does not have to be in the colored bars on the schedule. It can be in one 

of the footnotes. 

Dr. Stephens made a motion to approve the option reflecting the WG’s stated preference. 

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Dr. Bennett indicated that they have had the issue regarding preferences previously, and it is 

very difficult in the implementation phase when stated as a preference. She requested 

additional guidance. 

Dr. Messonnier pointed out that a preference implies that the WG would be okay with any of the 

groups receiving any schedule. They have been concerned about the language of preference 

due to implementation difficulties. If ACIP considered either schedule to be acceptable for 

either high-risk or healthy adolescents, but express a preference, they certainly could say that. 

The issue regarded how a clinician should interpret that. It already is difficult to articulate what 

ACIP meant by a Category B recommendation. Adding another layer of complexity on top of 

two different vaccines would make this harder. 

Dr. Lee said she thought the problem was the specificity for the vaccine product, and she was 

not used to thinking of it that way. She proposed that the vote be: 1) for persons at increased 

risk and for use during outbreaks, a preference for a 3-dose schedule of one product or a 2­

dose schedule of another product, but with the intent of it being in a shorter timeframe; and 2) 

when given to healthy adolescents, a preference for a 2-dose schedule of either product. 

Dr. Kempe said that alternatively, she thought it should be a recommendation because it 

already is problematic and this compounds the degree of complexity. She thought that 

particular statement should be a recommendation. 

Dr. Lee clarified that she meant “recommendation” and just wanted to flip it around in terms of 

the framing. 

Dr. Belongia emphasized that there is a difference between “preference” and 

“recommendation.” He thought it would be most clear for clinicians if stated that ACIP 

“recommends a 2-dose schedule for healthy adolescents.” 

Dr. Messonnier suggested that the members spend time during the break crafting revised 

language to pose for a vote. 

Dr. Moore said that operationally, while she appreciated the scheduling idea of bringing things 

together, since these are two products that cannot be interchanged unlike all of the other 

products that can, it would not be that much more complicated to make a specific FHbp 

recommendation in this case, because the other stands alone. While she recognized in terms 

of the schedule it is nice to work on the timing, but here she thought the recommendation could 

be narrower. 

Dr. Middleman (SAHM) requested that if there was a vote for a healthy adolescent to have a 2­

dose series, it could still be on the immunization schedule that a 3-dose series would be okay 

and would, therefore, be covered if there were a healthy adolescent who would like a 3-dose 

series. 

Dr. Messonnier indicated that the discussion for the next day regarding the schedule would 

allow for flexibility about what to put in the footnotes. 

Dr. Cohn added that there is always language in all of the statements that if someone receives a 

dose at the wrong time or received the second dose at 1 to 2 months, the third dose should be 

received to complete the schedule because the dose was not given at the right time. That is a 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

back-up safety net for people to complete to be fully protected if they did not receive the second 

dose after 6 months. 

Dr. Middleman (SAHM) expressed concern that this may penalize the provider in some cases in 

terms of coverage. 

Dr. Bennett suggested taking a half hour break to craft some specific language for the motion 

and vote. Upon returning, the new language was displayed for a revised motion: 

1.	 For persons at increased risk for meningococcal disease and for use during serogroup B 

outbreaks, 3 doses of MenB-FHbp should be administered at 0, 1-2, 6 months 

2.	 When given to healthy adolescents who are not at increased risk for meningococcal 

disease, 2 doses of MenB-FHbp should be administered at 0 and 6 months 

* If the second dose is given at an interval of <6 months a third dose should be given at 

least 6 months after the first dose 

Ms. MacNeil indicated that context would appear before the actual language in the Policy Note 

stating that there are two vaccines that are licensed for people aged 10 through 25 years in the 

US, and there is no vaccine preference. This also could include information about the current 

ACIP recommendation so that it is clear that there is a Category A recommendation for one and 

a Category B for the other. 

Regarding the footnote, Dr. Atmar asked whether there would be a minimal interval. For 

example, what if the second dose was given at 5.5 months. 

Ms. MacNeil replied that they could work on that language. 

Dr. Kempe wondered about the need for Bullet 2 since it was a Category B individual 

recommendation anyway. Bullet 1 was clear and was related to a Category A, so a firm 

recommendation made sense to her. 

Dr. Bennett said at first she suggested stating something such as “when a physician chooses to 

give to a healthy adolescent,” but she thought “when given to healthy adolescents” summed that 

up and implied that it would not be given to every healthy adolescent because it is a Category B 

recommendation and it would be in the context of the statement. 

Dr. Moore said that the WG would like to have further conversations about a booster dose for 

otherwise healthy adolescents immunized during a low-risk period of time who later find 

themselves involved in an outbreak setting or at high-risk. 

Ms. Stinchfield (NAPNAP) pointed out that one issue that seemed complicated was that risks 

were being lumped. There should be clarity about a person with an innate risk such as an 

immunodeficiency or a complement deficiency versus the immediate risk of a college outbreak. 

Those are two different risks that could have two different products and two different schedules. 

It would be helpful to keep those separated for clinicians. It might be that a clinic setting has 

one product, while a college and public health might have a different product. 

Dr. Bennett said her understanding was that this would be covered in the statement by creating 

the context. 

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Dr. Kimberlain (AAP) said he thought he was satisfied with what Dr. Kempe was asking about it 

being a Category B for the second portion of the second sentence. He asked for confirmation 

that for the first sentence, this was not a recommendation for Trumenba® over the other product. 

It simply was the part of the statement that dealt with Trumenba®. 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Ms. MacNeil confirmed this and indicated that each group at risk would be listed in the 

statement. 

Dr. Hunter asked whether there would be CDC guidance regarding how to handle persons who 

receive the 2-dose series when healthy, but then are exposed to an outbreak situation. 

Ms. MacNeil replied that this is something that can be discussed in the future. The next topic 

the WG wants to discuss is booster doses for people at increased risk, and this would fit into 

that category. 

Dr. Weber emphasized that increased risk could be increased risk of exposure or increased risk 

due to an immunodeficiency. His particular interest is in microbiologists in hospitals who are at 

increased risk of exposure, but who are normal immunologically. This would be long-term risk 

versus immediate risk, so he thought some clarification was needed regarding whether the 2- or 

3-dose schedule is recommended for those individuals. 

Ms. MacNeil replied that this would depend upon when the exposure would occur, but the 3­

dose schedule maximizes immune response, so if they are at increased risk, it may make sense 

for them to receive a 3-dose schedule. 

Ms. MacNeil confirmed that this was correct and that they would be very clear that there is no 

product preference. 

Public Comments 

Christina Hildebrand 

A Voice For Choice Advocacy 

I have three comments. The first is that you’re recommending this—I know you’re not saying it 

should be given to all healthy adolescents, but you’re recommending it for healthy adolescents. 

Yet, the efficacy of it that was shown in the slides showed that it had severe wear-off after 12 

months. It is not efficacious, or that efficacious after 12 months, I wonder why you are 

recommending it at that point, especially when you look at the number of side effects and 

deaths that come from the actual vaccine versus the number of deaths from meningococcal, 

which if you look at those numbers, the number of deaths from the vaccine are higher than the 

number of deaths that we’ve had from meningococcal. The other thing that I wanted to say is 

that as a public person and as a statistician, it really surprises me the data that you use. So, the 

base sizes of 12, 25, 60, 71 that were up on the screen earlier, you know, I don’t know if the WG 

uses different numbers or sees more information, but to me, those numbers are extremely small 

for studies that you are projecting onto the general population, even if it’s the general population 

of adolescents. Similarly you have—the largest study that you showed was Pfizer data, which is 

one of the companies that makes the vaccine. Of course, they’re going to say good stuff about 

it. You know, we’ve got ethics issues in the CDC. We know that. So sitting here and watching 

this data just really surprises me that this is the data that you’re working off to make vaccine 

recommendations. Thank you. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Dr. Bennett thanked Ms. Hildebrand for her comments and referred her to CDC’s SMEs for 

clarification. 

Vote: 2-Dose and 3-Dose Recommended Schedules for MenB-FHbp 

Dr. Stephens motioned to approve the language as revised. Dr. Romero seconded the motion. 

The motion carried unanimously with 14 affirmative votes, 0 negative votes, and 0 abstentions. 

The disposition of the vote was as follows: 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

0 Opposed: N/A 

0 Abstained: N/A 

VFC Resolution 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Santoli indicated that the purpose of this revision was to update the recommended 

vaccination schedule and intervals for serogroup B meningococcal vaccine. The resolution has 

two parts, and there are no proposed changes to the meningococcal conjugate vaccine section 

of the resolution. In the serogroup B meningococcal resolution, there is no change to the 

eligible groups. 

Eligible groups include: 

 Children aged 10 through 18 years at increased risk for meningococcal disease 

attributable to serogroup B, including:
 

 Children who have persistent complement component deficiencies (including 

inherited or chronic deficiencies in C3, C5-C9, properdin, factor H, or factor D or 

taking eculizumab [Soliris®]) 

 Children who have anatomic or functional asplenia, including sickle cell disease 

 Children identified to be at increased risk because of a meningococcal disease 

outbreak attributable to serogroup B 

 Children aged 16 through18 years without high risk conditions may also be vaccinated 

The recommended schedule and intervals are shown in the following table, summarizing the 

recommendation that was just approved: 

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Vote: VFC Resolution for 2-Dose and 3-Dose Recommended Schedules for MenB-FHbp 

Dr. Stephens motioned to approve the VFC Resolution for the 2-Dose and 3-Dose 

Recommended Schedules of MenB-FHbp. Dr. Belongia seconded the motion. The motion 

carried unanimously with 14 affirmative votes, 0 negative votes, and 0 abstentions. The 

disposition of the vote was as follows: 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

MenB (Bexsero®, 

GSK) 

Two doses, at least one month 

apart (0 and 1-6 month schedule) 

MenB (Trumenba®, 

Pfizer) 

Persons at increased risk for 

meningococcal disease and for 

use during serogroup B outbreaks: 

Three doses (0, 1-2, and 6 month 

schedule) 

Healthy adolescents who are not 

at increased risk for 

meningococcal disease: Two 

doses (0, 6 months)2 

Age Group Vaccine1 Dosing Schedule 

10–18 years

10–18 years 

1. Use of brand names is not meant to preclude the use of other serogroup B meningococcal vaccines where appropriate. 

2. If the second dose is given at an interval of <6 months a third dose should be given at least 6 months after the first dose 

For the recommended dosage and contraindications and precautions, the reader is referred to 

the product package inserts. 

Contraindications and Precautions can be found in the package inserts available at 

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM093833 

Statement Regarding Update Based on Published Documents 

[If an ACIP recommendation regarding Hepatitis B vaccination is published within 12 months 

following this resolution, the relevant language above (except in the eligible groups sections) will 

be replaced with the language in the recommendation and incorporated by reference to the 

publication URL.] 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

0 Opposed: N/A 

0 Abstained: N/A 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Herpes Zoster Vaccines 

Introduction 

Edward Belongia, MD 

Chair, Herpes Zoster Work Group 

Dr. Belongia updated ACIP on the Herpes Zoster (HZ) WG activities, reporting that there 

currently are two investigational vaccines: 

 HZ subunit vaccine (HZ/su) from GSK, which has been evaluated in non-immunocompromised populations 

and is currently being evaluated in immunocompromised populations 

 Inactivated vaccine (V212) from Merck that is being assessed in immunocompromised populations. 

Recently, the WG has received updates on the currently licensed vaccine, ZOSTAVAXTM, as 

well as presentations from manufacturers of the pre-licensure vaccines just mentioned 

regarding their current status and future plans. 

ACIP received a presentation during the June 2015 meeting on HZ epidemiology and interim 

Phase 3 efficacy studies on the HZ/su vaccine in adults ≥ 50 years old. Within the past month, 

results were published for the HZ/su vaccine in adults ≥ 70 years old. During this session, 

updates will be provided on HZ epidemiology and vaccine coverage and the final Phase 3 

efficacy study of HZ/su vaccine. In the coming year, the WG will be considering the policy 

options in anticipation of future licensed products. 

Herpes Zoster Background 

Kathleen Dooling, MD, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Dooling indicated that the objective of this presentation was to provide background on HZ 

disease and the current vaccine program for the purpose of information and discussion. She 

presented information on the clinical manifestations, evolving epidemiology, and prevention of 

HZ. There is a licensed vaccine for the prevention of HZ in adults, and two investigational 

vaccines are in development for the prevention of this disease. 

Varicella Zoster Virus (VZV) can cause two distinct forms of disease, primary infection that 

leads to chicken pox or varicella. Following primary infection, the virus establishes latent 

infection in the dorsal root ganglia near the spinal cord. Reactivation of the virus leads to 

shingles or HZ. The reactivated virus travels up the nerve root to discrete dermatomes to 

produce the characteristic shingles rash. Reactivation of virus may affect any dermatome of the 

body to produce the vesicular rash. The rash usually is unilateral and may involve as many as 3 

adjacent dermatomes. It typically arises over a 5 to 7day period, with resolution in 5 to 25 days. 

Occasional consequences of the rash may include secondary bacterial infections or 

transmission of VZV to susceptible individuals, resulting in chicken pox. 

About 90% of HZ episodes are associated with pain or discomfort. The pain is variable in 

character and intensity, and precedes rash onset in about 84% of cases. Pain without rash 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

typically lasts from 1 to 5 days, but it can be weeks. Localized pain in the absence of rash can 

lead to diagnostic dilemmas, such as unnecessary investigation, treatment, or even surgery. 

Another severe manifestation of HZ is involvement of the ophthalmic division of the trigeminal 

nerve. This occurs in approximately 15% of HZ cases. Ophthalmic involvement can cause 

chronic complications and in some cases loss of vision. 

Many people think of HZ as a self-limited illness. On the contrary, post-herpetic neuralgia 

(PHN), which is a common complication of HZ, can be a devastating illness and may persist for 

years. PHN is prolonged pain that lasts for at least 90 days following the resolution of rash. 

Approximately 10% to 18% of HZ patients will go on to have PHN. This pain may persist for 

months to years, and may be incapacitating. In terms of PHN prevention, antivirals and steroids 

have been shown to shorten duration of HZ, but do not conclusively reduce risk of PHN. 

Multiple modalities have been used for PHN treatment with partial or inconsistent efficacy, and 

have many side effects, especially in the elderly. 

The following quote is from an email recently received by CDC from a patient with PHN: 

“My shingles post herpetic neuralgia is still painful seven years after my shingles 

episode. My PHN is worse than my cancer and chemotherapy... [it] has made me 

depressed and suicidal in the past.” 

Regarding the epidemiology, HZ has an annual rate of approximately 4 cases per 1000 

population. That translates into about 1 million cases of disease in the US annually. The 

lifetime risk of developing HZ is about 1 in 3 and the age-adjusted rates appear to be increasing. 

Age appears to be the dominant factor driving incidence, with incidence in 80 year olds being 

about 10 times more than the incidence in children. Immunosuppression also is a risk factor. 

Blood malignancies, bone marrow transplant, and HIV all have been shown to increase the risk 

of HZ by up to 50-fold. In addition to being more common, HZ is more severe in the 

immunocompromised population, resulting in more disseminated disease and more 

hospitalizations. Ultimately, the underlying mechanism appears to be related to reduced cellmediated immunity, which allows VZV to reactivate or progress to HZ. 

Data derived from MarketScan, a large healthcare administrative database, demonstrate how 

the incidence of HZ increases with age. MarketScan contains records for hundreds of 

thousands of insured people. In the youngest age group, 0 through 14 years of age, the rate of 

HZ is about 1 case per 1000 population. The incidence increases with age sharply after age 50 

[Insinga et al., J Gen Intern Med. 2005, 20:748-53 (MarketScan administrative data]. 

Similarly, the incidence of PHN increases with age. In this case, data were derived from a 

population-based cohort in Olmstead County, Minnesota. Recall that only a fraction of 

individuals with HZ will go on to get PHN. In fact, PHN is rare in individuals younger than 50 

years of age, but risk increases steeply after age 60. An 80 year old is approximately 10 times 

more likely to get PHN than a 50 year old [Yawn, et al., Mayo Clin Proc. 2007; 82:1341-9 

(Olmsted County, MN)]. 

Over time, the incidence of HZ has increased for almost all age groups. This graph shows the 

increasing incidence by year from 1993 to 2014: 

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For adults 65 years of age and older, which is the top line on the graph, the incidence plateaued 

around 2007. For all other adults, the incidence seems to be increasing. For children, 

displayed on the bottom, there has been a downward trend since about 2005. The reasons for 

this increasing or plateauing incidence in adults are unknown, but it has been confirmed by 

numerous data sources. Looking specifically in children, precipitous drops of HZ incidence 

have occurred during the same time period, which is likely due to the direct effects of 

vaccination with VARIVAX®, as well as a decrease in circulating VZV, which has resulted in 

some children not ever having had a primary infection. Thus, they are not at risk for HZ 

[Adapted from Harpaz, ID week, 2015]. 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Regarding prevention, ZOSTAVAXTM was licensed by the FDA in 2006. Phase 3 clinical trials 

involved 38,500 non-immunocompromised adults ≥60 years old with a median follow-up of 3.1 

years. This vaccine consists of a live-attenuated Oka-strain VZV, which is about 14 times the 

concentration in VARIVAX®. Vaccine efficacy (VE) was 51% against HZ and 67% against PHN. 

SAEs were not more common in the vaccinated group; however, local reactions were more 

common. 

In terms of the results for vaccine efficacy in the Phase 3 clinical trial, overall, the vaccine was 

51% effective for the prevention of HZ and 67% effective for the prevention of PHN. The 

efficacy decreases with increasing age. The protection against HZ ranges from 64% for 

recipients in their 60s down to 18% for recipients 80 years of age and older. From the same 

Phase 3 clinical trial, efficacy against PHN was maintained against disease of longer duration. 

PHN was categorized according to how long the episode lasted, ranging from 30 days to 180 

days. ZOSTAVAXTM provided over 70% protection against PHN that lasted for 180 days 

[Oxman et al. Shingles Prevention Study, 2005]. 

In 2008, ZOSTAVAXTM was recommended by ACIP to be given as 1 dose in adults ≥60 years. 

As a live vaccine, it is contraindicated in immunocompromised persons. In 2011, there was no 

change to the ACIP recommendation following an FDA age expansion of the license to 50 

through 59 years of age. There were several reasons for this decision. First, there were 

vaccine shortages at the time that left people in the recommended group without access to the 

vaccine. This, combined with the fact that that the burden of HZ increases in people ≥60 years 

of age and over, resulted in maintaining the recommendation as it stood. After vaccine supply 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

issues were resolved, ACIP revisited the issue in 2013 and affirmed the recommendation for 

adults 60 years and older. This was based on data that showed waning of immunity. This 

graph shows the duration of protection provided by ZOSTAVAXTM: 

VE is shown by year following administration. The first four years of data were contributed by 

the Phase 3 efficacy trial previously discussed. Years 5 through 7 are contributed by a followon study, and years 8 through 11 by following a subset of the vaccinated cohort and a modeled 

control group. As shown in the above graph, efficacy decreases every year in the 5 years 

following vaccine receipt. The vaccine may not provide any significant protection after 8 years. 

As the risk of HZ and PHN increase with age, a higher burden of disease can be prevented with 

administration after 60 years of age and above [Tseng, et al., JID, 2016]. 

This graph also shows waning of immunity protection of ZOSTAVAXTM, but the data come from 

an observational study in a large health maintenance organization (HMO), Kaiser Permanente: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

In the Kaiser Permanente study, protection among all vaccinees started at 69%. However, by 

years 7 to 8 post-vaccination, vaccine protection decreased to 4% and it was not statistically 

significant [Tseng, et al., JID, 2016]. 

ZOSTAVAXTM uptake has shown slow and steady progress since 2007. By 2014, 28% of adults 

60 years of age and older in the US reported prior ZOSTAVAXTM receipt [2007: National 

Immunization Survey (Lu et al, Vaccine 27:882-7); 2008-13: NHIS (Am J Prev Med 40:e1-6 & 

MMWR February 5, 2016 / 65(1);1–36)]. In terms of why uptake has been sluggish, the price is 

high and there may be significant co-pays. In addition, the storage and handling of the vaccine 

requires freezing and reconstitution. This may dissuade some providers from carrying the 

vaccine. Also, supply shortages were a problem in the early years. However, this has since 

been resolved. For Medicare recipients, the vaccine is covered only by Part D and 

reimbursement can be complicated. Finally, the lower prioritization of adult vaccines as 

compared to the pediatric program and the general fragmentation of preventive care for seniors 

may contribute to low uptake. The first three factors described are vaccine-specific and may be 

ameliorated by modification of the existing vaccine or introduction of a new vaccine. The 

second three factors are system-related and must be addressed on a broader scale if there are 

to be meaningful increases in ZOSTAVAXTM vaccination. 

There are new vaccines on the horizon. The HZ/su vaccine developed by GSK is a vaccine 

consisting of VZV glycoprotein E as well as an adjuvant system. It is administered in 2 doses, 2 

months apart and it is refrigerator-stable. It was tested in a Phase 3 clinical trial in over 30,000 

non-immunocompromised adults 50 years of age and older. The primary endpoint was 

prevention of HZ, and the secondary endpoints were prevention of PHN, safety, and 

reactogenicity. In those Phase 3 clinical trials, VE for the prevention of HZ ranged from 97% for 

50 through 59 years olds to 91% for recipients 80 years and older. VE of at least 85% was 

maintained for all 4 years after administration in all age groups. This vaccine was found to be 

highly reactogenic. In study participants 70 years of age and older, 79% of vaccine recipients 

reported local symptoms compared to 30% of placebo recipients, and 12% of vaccine recipients 

reported Grade 3 reactions (e.g., symptoms that interfered with their daily lives) compared to 

2% of placebo recipients. 

Prevention of HZ in the immunocompromised population remains an unmet need. Two 

vaccines are in development for just this purpose. V212 developed by Merck is an inactivated 

formulation of ZOSTAVAXTM. It is a 4-dose series in persons 18 years of age and older. There 

is an ongoing Phase 3 efficacy trial of V212. HZ/su developed by GSK consists of a formulation 

of VZV glycoprotein E as well as an adjuvant system. It is administered as a 2-dose series in 

persons 18 years of age and older. There is an ongoing Phase 3 efficacy trial of HZ/su as well. 

Thus, there are exciting developments in the prevention of HZ. The WG anticipates deliberating 

on policy issues for non-immunocompromised and immunocompromised persons for several 

years to come. 

In conclusion, the epidemiology of HZ is changing. However, the reason for this is not fully 

understood. Approximately 28% of adults 60 years of age and older have been vaccinated with 

ZOSTAVAXTM in the US. Vaccines to prevent varicella and HZ are reducing the amount of 

circulating VZV in the US population. The two new vaccines for the prevention of HZ that have 

been developed and are being evaluated may further reduce the disease burden. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Update: Herpes Zoster Subunit (HZ/su) Vaccine 

Romulo Colindres, MD, MPH 

Global Medical Affairs Lead, Zoster 

GlaxoSmithKline 

Before beginning, Dr. Colindres indicated that he is a former EIS Officer and was really enjoying 

being back in Atlanta and connecting with old colleagues and friends, and being back on the 

CDC campus. He noted that he would be presenting on behalf of a very large team at GSK and 

many study investigators across the world on GSK’s HZ adjuvanted subunit vaccine, HZ/su, 

specifically with regard to recent trial results in people 70 years of age and older. 

Dr. Colindres highlighted the burden of disease of HZ, with approximately 1 million cases of 

disease being reported annually in the US1. Per CDC statistics, everyone has a 32% estimated 

lifetime risk of HZ1. With such a high percentage, it is not difficult to find someone who has 

been impacted by this disease. In his case, his 72 year old mother suffered from a very serious 

case of shingles 5 years ago, which included facial nerve involvement. Given her painful 

experience, he was sure she would be happy to learn about the new advances being made to 

prevent this disease. The risk of shingles also increases with age, such that above 85 years of 

age, the risk is 50%1. The most important risk factor is increasing age due to a natural decline 

in immune system function, immunosenescence, and also immunosuppression either because 

of disease or immunosuppressive therapy. HZ is generally not life-threatening. However, there 

can be some very serious complications, the most common being PHN with pain lasting greater 

than 3 months. Also, HZ opthalmicus can cause dangerous eye involvement, and there also 

can be cranial nerve palsies [

1CDC. Epidemiology and Prevention of Vaccine-Preventable 

Diseases. 13th ed. 2015]. 

The development of the HZ/su vaccine began at GSK 16 years ago at which time two target 

populations were chosen, adults ≥50 years of age and immunocompromised adults ≥18 years of 

age. From early in the development program and also specifically as Phase 3 clinical studies 

were being designed, several key aspirations were considered. The first was to achieve high 

vaccine coverage in persons ≥50 years of age. Because GSK did not think that was sufficient, 

they also wanted to increase VE in the older age groups ≥70 years and above. Again, these 

groups are the most susceptible and are at the highest risk for shingles and shingles 

complications. At the core of the aspirations was having a safe vaccine for all persons. This 

includes safety / efficacy in all persons at increased risk for HZ, including immunocompromised 

populations. The fourth aspiration was to have prolonged duration of protection. The final 

aspiration was ease of manufacture and reliability of supply. Many of these aspirations have 

been met. 

The following illustrates the composition of the non-live, adjuvanted subunit vaccine: 

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On the left in turquoise is the antigen, which is 50 μg of recombinant glycoprotein E. This is the 

most abundant protein found on the envelope of VZV, which elicits a specific cellular and 

humoral immune response. On the right is the adjuvant system, which is ASO1B. ASO1B is a 

liposome-based adjuvant system that contains immunostimulants MPL and QS-21. MPL 

enhances cellular and humoral immunity, while QS-21 stimulates Th1 cell-mediated immunity as 

well as cytotoxic T- lymphocyte activity. Synergistically, when MPL and QS-21 are combined, 

there is an enhanced proinflammatory response or innate immunity, as well as cellular and 

humoral response increases. Overall, this results in a faster, stronger, and longer lasting 

immune response [Dendouga et al. Vaccine 2012;30:3126–35; Garçon et al. Understanding 

Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam: Elsevier; 2011; chapter 4: 

p89–113; Dendouga et al. Vaccine 2012;30:3126–35; Grunewald et al. Science 

2003;302:1396–8; Mata-Haro et al. Science 2007;316:1628–32]. 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

In terms of background conclusions from the early phase studies, early phase safety and 

immunogenicity studies determined the combination of adjuvant and antigen and the dosing 

scheme. That led to the composition just described to be given as a 2-dose regimen. With 

regard to long-term immunogenicity in people 60 years of age and older, two doses of HZ/su 

induced a strong cell-mediated immune response of 19-fold higher than baseline at 1 month 

after dose 2. The immune response was maintained with age, including in adults ≥70 years of 

age. While a decline is observed in immune response after the first few years, this plateaus by 

year 4 and still remains 4 times above baseline 6 years post-vaccination [Chilbek R, Pauksens 

K, Rombo L, et al. Long-term immunogenicity and safety of an investigational herpes zoster 

subunit vaccine in older adults 2015; Vaccine, Volume 34, Issue 6, Pages 863-868]. 

Three Phase 3 efficacy studies make up the HZ/su development program. ZOE-50 (006)1 and 

ZOE-70 (022)2 are studies that evaluate HZ efficacy safety and immunogenicity in populations 

50 years and older and 70 years and older, respectively. These studies were begun in 2010 

and were recently completed. ZOE-50 results were presented to ACIP in 2015 and were 

published in the New England Journal of Medicine (NEJM). As a reminder, the primary results 

of ZOE-70 as well as pooled results from ZOE-50 and ZOE-70 were published in the NEJM in 

September 2016 [1Lal H. NEJM 2015;372:2087-96; 2Cunningham AL. NEJM 2016;375:1019­

1032]. Study 002 is evaluating HZ efficacy, safety, and immunogenicity in adults ≥18 years of 

age receiving an autologous hematopoietic stem cell transplant (aHCST). 

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In terms of the general study design and objectives for ZOE-50 and ZOE-70, both studies were 

randomized, placebo-controlled, multi-center studies running parallel in 18 countries across 

North America, Europe, Latin America, and Asia-Pacific. The primary objectives were HZ 

efficacy in persons ≥50 years of age or ≥70, respectively. Since the studies were conducted at 

the same sites, individuals who were 70 years or older were randomly assigned to either ZOE50 or ZOE-70. There also were pre-specified primary objectives for a pooled analysis, which 

included all subjects 70 years of age and older from both studies. These objectives were PHN 

efficacy and HZ efficacy. There were 16,160 subjects enrolled in ZOE-50 and approximately 

14,800 enrolled in ZOE-70. Subjects were randomized 1:1 in two groups. The vaccine group 

received 2 doses of HZ/su at 2-month intervals and the placebo group received 2 doses of 0.9% 

saline solution at 2-month intervals. There were 3 exclusion criteria: 1) having a previous 

episode of HZ disease, 2) having previous varicella or HZ vaccination, and 3) having an 

immunocompromising condition. 

In terms of the results in ZOE-50, for the primary objective, 6 cases were detected in the 

vaccine group versus 210 in the placebo group for a VE of 97% in individuals 50 years of age 

and older. That 97% was maintained independent of age, even in subjects 70 years of age and 

older with quite tight confidence intervals. The primary objective for ZOE-70 was to evaluate VE 

in the prevention of HZ, with secondary objectives to evaluate VE in the prevention of PHN and 

evaluate vaccine safety and reactogenicity. The pooled analyses has 2 pre-specified primary 

objectives, which were to evaluate VE in the prevention of PHN in subjects ≥70 years of age 

across both Phase 3 studies, and evaluate VE in the prevention of HZ in subjects ≥70 year of 

age across both Phase 3 studies. 

It is important to have a good understanding of the cohorts that were used for each of the 

analyses. The total vaccine cohort (TVC) included 13,900 subjects who all received at least 1 

dose of HZ/su. The follow-up time was 4 years. This was the primary cohort used for the safety 

analysis. The modified total vaccinated cohort (mTVC), excluded subjects not receiving dose 2 

or those who developed HZ within 1 month after dose 2. There were 13,163 subjects in this 

cohort. The mean follow-up time was 3.7 years. This was the primary cohort used for the 

efficacy analyses. The diary card cohort was a subset of TVC of approximately 1000 subjects, 

which was used for the reactogenicity analyses. Here are the ZOE-70 demographics results: 

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Another important aspect to look at is VE by year post-vaccination. From the pooled analysis, 

including all subjects 70 years of age and older, only 2 cases were detected in year 1 in the 

vaccine group versus 83 cases in the placebo group for a VE of approximately 98%. This year 

seems to be an outlier. In year 4, 4 years post-vaccination, VE was stilled maintained at 88%. 

Although these VE estimates are a snapshot, there is some consistency between years as can 

be seen by the overlapping confidence intervals. In terms of the pooled results of VE against 

PHN, the most important complication of shingles, there were 4 PHN cases in the vaccine group 

compared to 36 in the placebo group for a VE of 89% in individuals 70 years of age and older. 

Looking across all age groups, in general, VE is maintained with the exception of those 80 years 

of age and older in which there were too few cases to have statistical significance. This differs 

from what was observed in the ≥80 group for HZ where there was quite robust significance and 

quite high VE. 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

The mean age at dose 1 was 75.6 years, 54% of subjects were female, and there were virtually 

no differences between the vaccine and placebo groups for age, gender, region, or race. 

Approximately 20% of subjects were recruited from North America. 

In terms of VE against HZ overall and by age group as derived from the mTVC for ZOE-70, 23 

shingles cases were detected in the vaccine group compared to 223 cases in the placebo group 

for a VE of approximately 90%. This VE was maintained even in the older age group of 80 

years of age and older. The pooled ZOE-70 and ZOE-50 analyses include all subjects 70 years 

of age and older from both studies, the primary objective. These results are considered the 

most robust as there were approximately 3400 additional subjects who came from the ZOE-50 

study. With respect to the primary objective, 25 shingles cases were seen in the vaccine group 

versus 284 cases in the placebo group for a VE of 91%. Even among those individuals 80 

years of age and older, the VE of 91% was maintained with consistent and narrow confidence 

intervals. 

Turning to safety and reactogenicity as observed in ZOE-50 and ZOE-70, one observation as 

might be expected due to comorbidities and older age is that there were more SAEs and deaths 

reported from ZOE-70 than from ZOE-50. However, the important take-home message is that 

independent of coming from ZOE-50 or ZOE-70, there were no imbalances between vaccine 

recipients and placebo recipients for any of the endpoints (SAEs, pIMDs, or deaths). ZOE-50 

and ZOE-70 also provided some interesting information regarding reactogencity. In terms of 

solicited local symptoms reported 7 days post-vaccination of any grade comparing the 

vaccinated to the placebo group, as may be expected with an adjuvanted vaccine, injection site 

reactions were common and were more common in vaccine recipients than in placebo 

recipients. The median duration of these symptoms was 2 to 3 days, and most were mild to 

moderate in intensity. 

Looking specifically at reactogencity for Grade 3 reactions (greater than 100 mm for redness 

and swelling and impeding normal activities for pain) for local symptoms, 8% or less of Grade 3 

reactions were reported. However, these were reported more often in vaccine recipients than in 

placebo recipients. The mean duration for these symptoms was 1 to 2 days. Looking at 

solicited systemic symptoms reported 7 days post-vaccination of any grade, the 3 most common 

systemic symptoms were fatigue, headache, and myalgia. These were more commonly 

reported in the vaccine recipients compared to placebo recipients. Most were mild to moderate 

in intensity, and the median duration was 1 to 2 days. Regarding the Grade 3 systemic 

symptoms reported, 6% or less were reported across the study. They were more frequent in 

vaccine recipients compared to placebo recipients specifically for fatigue, headache, myalgia, 

and shivering. The median duration was 1 to 2 days. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Regarding compliance with the second dose, for ZOE-50 compliance with the second dose was 

96% for both vaccine and placebo groups. For ZOE-70, it was 95% or 96% for vaccine and 

placebo groups. Essentially across the board, there was very high second dose compliance. 

In summary of safety and reactogenicity for ZOE-70 and ZOE-50 / ZOE-70, no safety signal has 

been detected. There was no imbalance in the incidence of safety endpoints (SAEs, pIMDs, 

deaths) were observed between the HZ/su and placebo groups. Additionally, AEs and safety 

endpoints were as expected in this patient population. Local and systemic reactions to HZ/su 

were common in the first 7 days after vaccination. The large majority were of mild-moderate 

intensity and of short duration. 

In summary of efficacy for ZOE-70 and ZOE-50 / ZOE-70, ZOE-70 VE in adults 70 years and 

older was >90% for the prevention of HZ. These results are fairly consistent with the previous 

97% VE in this age group from ZOE-50 trial. In the pooled analyses, considered to be the most 

robust analysis, VE for the prevention of HZ in adults 80 years and older was 91%. HZ/su VE of 

88% was demonstrated through year 4, and exhibited similarly high efficacy of 89% in the 

prevention of PHN in individuals 70 years and older. 

With respect to upcoming evidence generation, GSK has quite a bit of ongoing evidence 

generation activity. There is a revaccination study that is evaluating the immunogenicity, safety, 

and reactogenicity in individuals with a history of ZOSTAVAXTM immunization at least 5 years 

prior who were subsequently vaccinated with HZ/su. There are a series of co-administration 

studies to evaluate the immunogenicity, safety, and reactogenicity of the vaccine when coadministered with quadrivalent influenza, pneumococcal polysaccharide vaccine 23 (PPSV23), 

and Tdap. There also is a duration of protection study in which efficacy, safety, and 

immunogenicity persistence are being assessed over a long period of time up to 10 years postvaccination as an extension of the ZOE-50 and ZOE-70 studies. 

The other exciting news is that GSK plans to submit a BLA for Center for Biologics Evaluation 

and Research (CBER) review of the candidate HZ/su vaccine before the end of 2016, with the 

expected indication of prevention of HZ in adults 50 years of age and older. GSK is very proud 

of HZ/su and believes this vaccine not only has the real potential to improve the prevention of 

shingles and its complications, but also could shed light on the way future vaccines are 

developed to overcome the challenges of decreasing immunity in older adults and the elderly. 

Discussion Points 

An inquiry was posed regarding whether GSK planned to assess the use of HZ/su vaccine in 

individuals who have a previous history of HZ. In addition, there was a low number of Black 

participants in the study of only 1%. 

Dr. Colindres replied that GSK has conducted a study looking at vaccinating individuals who 

had a previous episode of HZ disease, which should be published soon. The results were that 

the vaccine was immunogenic and safe. With regard to the percentage of Black participants in 

the study, there are two considerations. The first is that this study was conducted worldwide in 

a lot of countries throughout the world including Europe, Asia-Pacific, and Latin America. 

Looking at that number for North America in the US, it would be approximately 4%. It is still less 

than the percentage of African Americans in the US population, but it is slightly higher. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Regarding ZOE-50, Dr. Middleman (SAHM) pointed out that slide 9 showed that the efficacy 

among those ≥70 is 97.9% with a pretty nice confidence interval. In ZOE-70, the efficacy for 70 

through 79 years was 90% with still a pretty tight confidence interval. She asked whether there 

had been any thought about why the two studies would have different VE findings. 

Dr. Colindres responded that he did not have a magic answer to that, other than it was what 

came out in the clinical study. There was some degree of overlap in the confidence intervals, 

which accounts for some of it. 

Dr. Kimberlain (AAP) noted that on the pooled analysis for HZ, the sample sizes were in the 

8200 to 8300 range. However, the PHN pooled analyses that increased to 13,000 for the 

sample sizes. He asked whether Dr. Colindres could explain why. 

Dr. Colindres replied that this essentially was because the 50 year old group also was included. 

For the pooled analyses, which would include the primary objective, the other sample size of 

8000 or so is correct. This sample size included those 50 years and above, which included all 

subjects including the 50. 

Dr. Atmar noted that the frequency of PHN in persons over 80 years of age was remarkably 

lower in the placebo group compared to younger age groups where it was about 50% to 60% of 

people who develop HZ. He asked whether there was an explanation for that. 

Dr. Colindres replied that he did not have an explanation of why it was lower in those 80 years 

of age and above, although they did observe that as well. The prevention of PHN was clearly 

associated with decreased incidence of HZ disease, so clearly one was linked to the other. 

Dr. Walter requested clarification regarding whether the efficacy analyses included only the 

period following 1 month after the second dose, and if he had any information on the distribution 

of cases that occurred following the first dose in that time period. 

Dr. Colindres responded that the efficacy analyses included after 30 days essentially, and there 

were under 20 cases during that time period following the first dose. 

Dr. Messonnier asked whether Dr. Colindres to provide some sense of the timing of when data 

would be available from the upcoming evidence generation, and Dr. Bennett asked about 

vaccination of people who have previously received HZ vaccine. 

Dr. Colindres replied that they are actively working on the revaccination study and should have 

results by about April or May of 2017. They are working closely with the ACIP HZ WG to have 

that information reviewed as soon as possible. The co-administration studies are completed 

and in the analysis phase. An abstract of the influenza co-administration study will be 

presented during IDWeek and showed quite good results. The duration of protection study is 

still a way off. The study of people who previously have had HZ has been completed, and GSK 

is in the process of writing the manuscript. 

Dr. Hahn (CSTE) asked whether Dr. Colindres had data on AEs from first dose compared to 

second dose, and if a person had an AE the first time, did they had a worse reaction from the 

second dose. 

Dr. Colindres indicated that there does seem to be some correlation, but GSK is still in the 

process of analyzing these data. They will share it as soon as it is available. 

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YF vaccine is a live-attenuated viral vaccine produced in chick embryos. There are 4 WHOprequalified vaccines available globally. Vaccine Prequalification is a process established by 

WHO to ensure the quality and safety of vaccines provided through the United Nations (UN) for 

use in national immunization programs. There is only one YF vaccine licensed for use in the 

US, which is YF-VAX® that is manufactured by Sanofi Pasteur. YF-VAX® is not WHOprequalified and is, therefore, not part of the global supply. YF vaccine is the only one for which 

proof of vaccination can be required by countries from arriving travelers under International 

Health Regulations (IHR) of 2005. 

 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Whitley-Williams (NMA) noted that in addition to under-representation of Blacks in the study, 

she did not see Hispanics in the US population. While she recognized how difficult it can be to 

conduct studies in the US, she emphasized that studies should reflect the population as it is 

represented in the US, particularly regarding immunogenicity and AEs. If this was rolled out and 

for whatever reason there was an increase in AEs in a particular ethnic group, this could 

negatively impact an already challenging adult immunization system. 

Dr. Friedland (GSK) indicated that GSK works extremely diligently to identify investigators and 

patients who are representative of the US population in its clinical trials. These results are not 

different from other clinical trials with other vaccines. It is very difficult to identify patients and 

investigators who can enroll in these clinical studies in order to have representative populations. 

GSK is not giving up and will continue to work on this. 

Yellow Fever Vaccine 

Mark Gershman, MD 

Travelers’ Health Branch 

Division of Global Migration and Quarantine 

National Center for Emerging and Zoonotic Infectious Diseases 

Centers for Disease Control and Prevention 

Dr. Gershman reminded everyone that Yellow Fever (YF) is caused by the YF virus, which is in 

the genus flavivirus. This virus is transmitted predominantly by Aedes mosquitoes. YF disease 

is endemic in sub-Saharan Africa and tropical South America. Asymptomatic infection occurs in 

most people. When clinical disease occurs, it ranges from mild febrile illness to severe disease 

with jaundice and hemorrhage, and can be fatal. Outbreaks occurred in 2016 in areas of Africa 

where cases had not been reported for decades, with the most notable being a large outbreak in 

Angola that is now subsiding. 

Regarding the global YF vaccine supply in 2016, 6 million doses of YF vaccine are placed in a 

global emergency stockpile annually. This stockpile is managed by the International 

Coordinating Group (ICG) on Yellow Fever Vaccine Provision (WHO, UNICEF, MSF, Red 

Cross/Red Crescent). The emergency response to large outbreaks in Africa this year depleted 

this stockpile several times. Consequently, YF vaccine doses allotted for childhood and 

prevention campaigns were rerouted for response efforts. Also, as a dose-sparing measure in 

the face of global shortages, fractional doses of YF vaccine were used in Democratic Republic 

of the Congo (DRC) for preemptive vaccination of residents of Kinshasa. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

In the US, YF vaccine is used to vaccinate people travelling internationally, including the 

military. This is for travel to countries where there is risk of YF virus transmission, and for travel 

to countries that have entry requirements for proof of YF vaccination as allowed under IHR 

2005. Also, YF vaccine is used to vaccinate laboratory workers potentially exposed to YF virus 

in their line of work. Regarding the YF vaccine supply in the US, historically, intermittent 

manufacturing issues have led to temporary supply shortages. Since the end of 2015, there has 

been an ongoing YF vaccine shortage in the US, with ordering restrictions in place this entire 

time. This was compounded by the anticipation of additional demands on the vaccine supply for 

travel to the Brazil Olympics this past summer by athletes, official delegations, and tourists. 

In conjunction with the large YF outbreak in Africa and global supply issues, concerns about the 

US YF vaccine supply led to the initiation of stakeholder discussions in spring 2016. The focus 

of these discussions was how to assure a stable YF vaccine supply for travelers, military, and 

response personnel in the US. Participants included CDC, Sanofi Pasteur, FDA, and the 

Department of Defense (DoD). The options to assure the US YF vaccine supply reviewed in 

these discussions included the following: 

 Maintaining the status quo by relying on the release of new YF-VAX® lots currently in 

production 

 Implementing an Expanded Access Investigational New Drug (IND) application to allow 

for importation and use of YF vaccine licensed outside the US 

• This vaccine would be STAMARIL®, which is manufactured in France by Sanofi 

Pasteur and is licensed and marketed in more than 70 countries 

 Using fractional dosing of YF vaccine as was done in the DRC 

At present, the status of these options for the US YF vaccine supply is that YF-VAX® lots 

currently being produced are scheduled to be released before the current inventory is 

exhausted. Notably, the current inventory is lasting longer than anticipated because the level of 

increased demand for the Olympics did not occur. Current ordering restrictions for YF-VAX® 

would remain in place to help modulate the future depletion of current inventory. A contingency 

plan is being developed with submission of an IND application to import and use STAMARIL®, 

the YF vaccine licensed outside the US. The IND application is presently under a 30-day review 

by the FDA. The IND protocol, including training of clinicians, would be implemented should 

there not be an adequate US supply of YF vaccine. Fractional dosing was not considered to be 

a viable option based on limited data and many uncertainties. 

In conclusion, in 2016, limitations occurred in both the global and the US YF vaccine supply. 

Contingency plans are being developed for the US YF vaccine supply. These plans will be 

enacted as needed based on demand and supply. 

Discussion Points 

Dr. Belongia asked for additional explanation about how the IND works with a vaccine licensed 

in another country, and what the protocol is. 

Dr. Gershman replied that the protocol is basically the plan regarding how to get the vaccine 

distributed to the clinicians who will use it, the conditions of distribution, the conditions of 

monitoring safety, et cetera. It is not an experimental protocol. Expanded access is a clinical 

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Dr. Greenburg (Medical Affairs, Sanofi Pasteur) agreed with Dr. Gershman’s summation. This 

is a clinical protocol as opposed to a study per se, such as a clinical trial with hypotheses and 

specific statistical questions being asked. Instead, it is a mechanism that is reviewed and 

approved by the FDA to import STAMARIL® as an unlicensed product into the US and distribute 

it to clinicians throughout the US at specific sites that use a lot of YF vaccine. These will be 

clinicians who are used to administering YF vaccine, who would administer the vaccine as they 

normally would with YF-VAX® and monitor / report safety issues to Sanofi Pasteur as the 

manufacturer and to the FDA. Otherwise, use of the vaccine is fairly routine with some 

additional safety follow-up. 

Dr. Gershman added that the challenge with this is that it is a unique vaccine and a unique 

situation. Over 5000 civilian clinics administer YF vaccine, so it would not be practical or 

achievable to distribute STAMARIL® to all of those clinics. It would be virtually impossible. Part 

of the protocol involves how site selection is accomplished. What seems to be a reasonable 

situation has been worked out to distribute to those clinics that appear to be the top users by 

volume, and such that geographical access is maintained for people in all states. It is a delicate 

balance, because the amount of work involved is quite a lot. However, the vaccine needs to be 

accessible in order to prevent the importation of a potentially fatal disease. 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

protocol, similar to that for an orphan drug, to supply a vaccine or drug that otherwise would not 

be available and is deemed to be absolutely necessary. He deferred to Dr. Sun from the FDA 

or representatives from Sanofi Pasteur to offer further information, given that Sanofi Pasteur 

wrote the protocol. 

Dr. Hunter asked whether the current situation with the US supply being separate from the 

global supply was a conscious policy decision, or if it developed historically for market reasons. 

Dr. Gershman replied that he thought it had developed historically for market reasons because 

in general, YF vaccine is used for two main purposes: 1) for international travelers, in which 

case it is used only in the country in which it is produced, which is a very circumscribed market; 

and 2) for vaccines provided through the UN for use in national immunization programs, which 

go through the rigorous WHO Vaccine Prequalification process to ensure the quality and safety 

of those vaccines for mass vaccination campaigns. Sanofi Pasteur did not pursue WHO 

prequalification for the US-manufactured vaccine YF-VAX®, but justifiably so. Why would it 

need to be done? It is a lengthy and expensive process. STAMARIL® is produced in France 

and is one of the WHO prequalified vaccines used globally, including in routine infant 

immunization programs and in mass vaccination campaigns - preemptively, and in response to 

outbreaks. 

Dr. Plotkin (Vaccine Consultant) apologized at this late hour, but wanted to make a specific 

request since he did not know when YF would come up again. He requested that CDC 

reconvene the YF WG to reconsider its recommendation regarding YF vaccine boosters, and 

indicated that he had data. In February 2016, the YF WG recommended that revaccination is 

unnecessary for YF. They stated and printed that 92% of vaccinees are seropositive at 10 

years, that there is a paucity of vaccine failures, and evidence of seropositivity. Recently, an 

article was published by Amanna and Slifka in which they reviewed the literature and concluded 

that immunity is lost in 20% to 33% at 10 years, and that children are at greater risk for losing 

their seropositivity. He quoted from their article, “An extensive study examining cases of yellow 

fever in Brazil has provided much needed insight. In this study, patients were not only queried 

about their vaccination status, but also asked whether they had been vaccinated within 10 years 

prior to contracting yellow fever. There were 831 cases of yellow fever identified between 1973 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

and 2008. Vaccination status was unavailable for 372 of the patients, but the remaining 459 

cases had received prior yellow fever vaccination, and yet still contracted yellow fever. Since all 

of the cases of yellow fever were virologically confirmed, we believe that this is likely to be a 

more accurate representation of vaccine failures than the previous estimate of only 23 

worldwide vaccine failures.” Then the comment that “52% of those had been vaccinated more 

than 10 years previously” [Ian J. Amanna & Mark K. Slifka, Questions regarding the safety and 

duration of immunity following live yellow fever vaccination, Pages 1519-1533 | Received 01 

Mar 2016, Accepted 02 Jun 2016, Accepted author version posted online: 08 Jun 2016, 

Published online: 20 Jun 2016]. Dr. Plotkin recommended that the WG read this paper. There 

also is a study from Brazil specifically in children, which shows seroconversion rates after the 

first vaccination of only about between 80% and 85%. Michael Tauraso reviewed the situation. 

It is true in the abstract he says that duration of immunity is good, but looking at his table, for 

those studies in which there were more than 100 people involved, the persistence was 76% at 

17 years, 81% at 30 years, 75% at 10 years, 69% at 4 years, and 65% at 10 years. There was 

no study of Africa where YF is epidemic, so the duration of immunity is unknown in an African 

population. He thinks that duration of immunity of the YF vaccine has been exaggerated. He 

thought this should be reevaluated in light of all of the data available, not simply those that 

apparently were used by the initial group. 

Dr. Bennett thanked Dr. Plotkin for his comments and said she thought the issue would be taken 

into consideration by the WG. 

Ms. Pellegrini asked whether there was any explanation for why YF has reemerged so 

suddenly and so aggressively in parts of Africa. Over the last couple of years, there seem to 

have been a number of cases where flaviviruses have done this, or left continents and wreaked 

havoc. She wondered whether they should be worried about YF perhaps spreading to 

additional areas. 

Dr. Gershman replied that while he did not think anyone knew for sure, he thought it was 

partially a result of a combination of global climate change, and El Niño cycles that are periodic 

and normal. This can lead to an increase in the density of mosquito vectors, which has occurred 

during a time of growing populations in urban areas in Africa. This is an urban cycle YF 

outbreak that has been so severe in Africa. In general, there are several different cycles of YF 

virus transmission. The urban cycle has as its vector the Aedes aegypti mosquito, and involves 

person-to-mosquito to person transmission of the YF virus. The sylvatic cycle is jungle YF 

where people wander into the jungle and are bitten randomly by mosquitos that usually prefer to 

bite monkeys. As more roads are being built, more access is created to people from areas 

where they might be exposed to YF virus by the jungle transmission cycle, to urban areas, 

where they can then introduce it to heavily populated areas with dense levels of Aedes aegypti 

mosquitos. He thinks it is a host of all of these factors. 

In the context of the events that occurred, Dr. Thompson (NVAC) requested further information 

about what occurred to cause the supply disruption and whether anything is being done to 

increase the safety stock to address this. 

Dr. Gershman replied that it is a manufacturing issue, and deferred to the Sanofi Pasteur 

representative to provide more details. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Julian Ritchey (Sanofi Pasteur) confirmed that it is a manufacturing issue and for some time, 

Sanofi Pasteur has been looking to move to a new manufacturing facility. The current 

manufacturing facility is older, and they are in the process of making that transition and making 

it seamless. 

Regarding Ms. Pellegrini’s question, Dr. Sun (FDA) added that YF cases from the recent 

outbreak in Africa were imported to China. Even though the mosquito that transmits YF has 

been endemic in Asia, Asia has not had YF. This is an enigma for flavivirology. Travelassociated YF that is imported from areas of outbreak is of great concern. Regarding IND, Dr. 

Sun explained that the Expanded Access IND is a mechanism by which unapproved products 

can be made available for use, and in this case, for wider use. The same mechanism was used 

for Bexsero® for MenB in university outbreaks. There are various versions of the Expanded 

Access IND. There is one for products that are to be licensed, and one for products that are not 

headed for licensure. They are dealt with somewhat differently, but the basic principle is that it 

is still considered an unapproved product and, therefore, the transport across state lines has to 

be under IND. In addition, there has to be a streamlined approach to collection of AEs. 

Day 1: Public Comment 

Dr. Stanley Plotkin 

Vaccine Consultant 

Once again I apologize for keeping the committee, but I just don’t have any choice in the matter 

so to speak. What I am now urging on the committee is to form a Lyme Disease Vaccine WG. 

That a Lyme disease vaccine is sorely needed I think is without question. The CDC itself 

estimates 300,000 annual cases, and there are another 20,000 estimated in Europe. Carditis, 

neurological complications, and rare deaths occur. I have spoken to this committee before and 

mentioned that one of my own sons had a life-threatening case of Lyme carditis. At any rate, 

the original vaccine that was licensed in the late 90s worked quite well in terms of its efficacy, 

although boosters were needed because of the mechanism of the OspA (outer surface protein 

A) antigen that was in the vaccine. Unfortunately, and I say this carefully but clearly, that CDC 

did not support the original Lyme disease vaccine. That was one of the reasons why it was 

taken off of the market. Another reason was that the manufacturer did not do a pediatric study 

until it was too late. Then there was a questionable safety signal, which was never supported 

by VAERS analysis, was never supported by laboratory analysis, but was enough to decrease 

sales and the manufacturer took it off. I should mentions as far as the pediatrics is concerned, 

the study that was done late in the game shows that if anything, children responded about 10 

times better to the vaccine than did adults. So, the question now is can we have a new 

vaccine? I’ve been working with potential Lyme vaccine manufacturers, and I should say clearly 

that I have no financial interests in this whatsoever. But, they do not know if ACIP is interested 

and will make a positive recommendation. Clearly, ACIP cannot make a recommendation 

without having an actual vaccine. But, it could indicate interest in having one. I think a Lyme 

Disease WG to consider the target product profile and to meet with potential new vaccine 

manufacturers, and there are candidate vaccines, would be very desirable. The situation I think 

is similar to the rotavirus situation. If you recall, the original rotavirus vaccine was taken off of 

the market because of intussusception. Then the issue for the manufacturers, and I was 

personally involved in this, was will a new vaccine be recommended? It was clear at the time 

that ACIP wanted to prevent rotavirus disease and, therefore, two manufacturers undertook to 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

make new vaccines, which ultimately were licensed. Again, and lastly, I hope that the ACIP will 

consider forming a Lyme Disease Vaccine WG to indicate that they have an interest in an 

eventual vaccine. In 2000, the IOM did an analysis of what vaccines—that is, what diseases for 

which we need vaccines, what are the first priorities for developing vaccines? That was a very 

important document. That had a major effect on the manufacturers in terms of choosing targets. 

That sort of analysis is really needed. NVAC should do it, but they won’t. The ACIP could do it 

by various mechanisms, but again, has not undertaken to do that. Thank you. 

Dr. Bennett responded that Dr. Plotkin posed an interesting problem, but that it probably was 

beyond the purview of the ACIP to develop a WG to advocate for the development of a vaccine. 

However, it is not beyond the purview of the CDC or the SMEs at the CDC. This is an 

overarching problem in the US. How do we decide which vaccines we advocate for the 

development of? There is not a very good systematic approach to this. 

In response to whether this would fall under NVAC’s purview, Dr. Birkhead (NVPO) said he 

thought that the NVPO addresses the development of new vaccines. However, he was not 

aware of a formal mechanism by which recommendations are made for vaccines that are of 

interest for further development. 

Dr. Thompson (NVAC) indicated that NVAC has been very interested in recent meetings in the 

area of vaccine innovation. She thought this would fall into that category as it would be a new 

vaccine. NVAC certainly is assessing all of the incentives that the whole system faces with 

respect to innovation in the vaccine area, so she thought this was something NVAC could take 

up as a question, but in the context of the broader theme. One issue that Dr. Plotkin raised that 

has been raised by others to NVAC is the fact that manufacturers or developers in general 

would like some assurance that there would be a market for a product. That is very hard for any 

advisory committee to give. The concept of target profiles is interesting and is worthy of 

exploration, and certainly is something that NVAC could consider. Perhaps ACIP could in some 

way consider that as well at some point. 

Christina Hildebrand 

A Voice For Choice Advocacy 

To finish off the evening, I wanted to come back to a few comments that I made earlier and just 

expand on them. The first one is, you know, looking at all of the data that was presented today, 

it was either really small base sizes or it was by the pharmaceutical companies, which is not 

independent research by any means. I really urge the CDC to do independent research that is 

not the CDC or the pharmaceutical companies doing research, because both of you get money 

out of this, and so we need an independent research body doing research. We’ve got 12 CDC 

researchers who came out today questioning the ethics of the CDC, and the infiltration of money 

into the CDC and into our government. We know that pharmaceutical companies are the 

largest lobbying force out there. We also have one CDC whistleblower, Dr. William Thompson, 

who has shown that there’s been fraud at the CDC. He’s shown that there has been fraud on 

the MMR studies. There’s also, you know, efficacy research on the MMR. There’s a lawsuit 

right now questioning the efficacy of the MMR. I just, you know, I look at this data and I look at 

what you’re doing here at the ACIP and at the CDC and I just ask that independent research is 

done or that you use the independent research that is out there, because using paid for 

research or your own research just isn’t good enough. Thank you. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Zika Virus Update

Ms. Stacey Martin 

National Center for Emerging and Zoonotic Infectious Diseases 

Centers for Disease Control and Prevention 

Ms. Martin explained that Zika virus is an ribonucleic acid (RNA) flavivirus related to dengue, 

YF, Japanese Encephalitis (JE), and West Nile Virus (WNV). Transmission to humans is 

primarily by Aedes (Stegomyia) species mosquitoes. Infection is typically asymptomatic or 

causes mild dengue-like illness. However, recent outbreaks have identified new modes of 

transmission and clinical manifestations. 

Zika virus was first isolated from a sentinel rhesus macaque monkey in Uganda in 1947. Before 

2007, only sporadic human disease cases were reported from Africa and Southeast Asia. In 

2007, the first Zika outbreak was reported on Yap Island, Federated States of Micronesia. In 

2013–2015, more than 30,000 suspected cases were reported from French Polynesia and other 

Pacific islands. Local transmission was first identified in the Americas in May 2015 and 

subsequently spread across the region. 

As of October 13, there are 47 countries and territories in the Americas that have confirmed 

mosquito-borne transmission of Zika virus. The map below provides a timeline of the first 

reports of local transmission with Brazil confirming its first case prior to October 2015 and the 

US confirming its first case this summer. The table on the right reflects the number of locally 

transmitted Zika virus disease cases reported to the Pan American Health Organization (PAHO) 

by country in the Americas, now in excess of 660,000: 

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Approximately 60% of the total cases were reported from two countries, Brazil and Colombia. 

Of note, most of the reported cases are suspect cases and only 23% of cases are laboratoryconfirmed. Most suspected and confirmed locally transmitted cases reported to PAHO, as of 

October 2016, were reported from South America (73%), followed by the Caribbean (18%), and 

then Central America (8%). 

Zika virus disease was made a notifiable condition in Brazil in February 2016. For this reason, 

temporal trends of cases are only available in 2016. There was an increasing trend starting in 

January that peaked in February. Since then, there has been a steady decline in both 

confirmed and suspected reported cases. Zika became a reportable condition in Columbia in 

October 2015. Reported cases began to increase in August 2015 and continued until early 

February 2016. Reported cases have declined since the peak. In Mexico, the first confirmed 

case was reported in late 2015. In 2016, Mexico reported an increase in cases that peaked in 

August. As of epidemiology week 42, and given the expected lag in reporting, it was too soon to 

say whether they are experiencing a decline in cases. CDC also has recently learned about 

cases being identified in communities along the border with Texas. 

In the US, a total of 3892 travel-associated cases have been reported to ArboNET as of October 

12th. Of these travel-associated cases, 98% were reported from the States. For locally 

acquired cases, a total of 25,999 cases have been reported, and 98% of these were reported 

from Puerto Rico. In the States, 128 locally-acquired cases have been reported to ArboNET, all 

from Florida. 

The following map shows laboratory-confirmed Zika virus disease case reported to ArboNET by 

state or territory, with 49 states having reported cases. The highest reporting states are New 

York and Florida, each reporting over 20% of the cases, followed by California and Texas. All 

other states have reported less than 5% of the total cases: 

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Between January and October 2016, there have been a total of 3775 travel-associated cases 

and 137 locally acquired cases in the US reported to ArboNET. The epi curve suggests the 

number of reported cases peaked in July, but there is a lag in reporting. Also, the US reported 

its first locally transmitted case in June from Florida. Florida continues to report locally 

transmitted cases. The majority of cases occur in adults, with the highest number of cases in 30 

through 39 year olds. Travelers returning from the Caribbean represent the highest proportion 

of travel-associated cases, followed by travelers from Central America, South America, and 

North America. 

Puerto Rico reported its first case at the end of 2015. The number of reported confirmed cases 

increased from January through August of 2016. Following the peak, the weekly number of 

reported cases has declined. The Puerto Rico Department of Health has reported over 28,000 

cases. As shown in the following map, the cases are distributed throughout the island. This is 

likely a significant underestimate of the true number of infections, since the clinical presentation 

of Zika virus infection is typically mild or asymptomatic: 

As previously mentioned, Florida has reported over 100 locally acquired Zika cases. The first 

area to be identified was the Wynwood neighborhood of Miami-Dade County, followed by Miami 

Beach, and then most recently, Little River, also in Miami-Dade County. To summarize, Florida 

has experienced sporadic locally acquired cases in multiple counties in Florida. Many of these 

are believed to be single transmission events without further spread. The three areas 

highlighted on the following maps were found to have multi-person transmission, which 

prompted Florida and CDC to recommend that pregnant women avoid travel to those areas: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

In Wynwood, state and local officials appear to have successfully ended local transmission after 

aerial spraying and other mosquito control efforts. As of October 17th, Florida has reported 160 

cases of locally transmitted infections. Concerns about low levels of transmission outside of the 

three designated areas zones prompted Florida and CDC to state that pregnant women and 

their sex partners may consider postponing nonessential travel to all parts of Miami-Dade 

County. As of October 19th, CDC began recommending laboratory testing for all pregnant 

women who have had exposure to all areas of Miami-Dade County after August 1st. 

Before ending, Ms. Martin provided a high-level overview of Zika virus vaccine development 

activities. She indicated that a US government interagency working group that includes 

members from the Assistant Secretary for Preparedness and Response (ASPR), National 

Institutes of Health (NIH), Biomedical Advanced Research and Development Authority 

(BARDA), FDA, CDC, and Walter Reed Army Institute of Research (WRAIR) was established 

to: 1) evaluate promising candidate vaccines for safety, immunogenicity, and efficacy; 2) ensure 

availability of one or more candidate vaccines in 2018 for emergency use in US population at 

high risk of exposure or disease; and 3) work with partners to commercialize vaccines for broad 

distribution by 2020. Currently, there are many vaccine candidates in preclinical development 

which will be presented to ACIP at a later date. There are expected to be four vaccines in 

phase 1 clinical trials by the end of 2016, and phase 2 studies are scheduled to begin in 2017. 

Discussion Points 

Given that about 80% of Zika cases are asymptomatic, Ms. Pellegrini asked whether CDC 

thinks it is possible or likely that the 25,000 plus in Puerto Rico could be 20% or possibly even 

less for people not seeking care at all in terms of the actual number of infections in Puerto Rico. 

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Ms. Martin stated that it is possible. The only data CDC has that provides a ratio of 

symptomatic to asymptomatic cases is from Yap Island. It is believed to be about 1:4. The 

number of reported cases is likely a dramatic underestimate of the true burden of disease on the 

island. 

Once the epidemic curve has run its course in a population, Dr. Hunter asked what the role of 

vaccination would be in a country that is going to be endemic versus a country that has different 

areas that are going to be endemic and others that are not. 

Ms. Martin replied that there always are likely to be susceptible populations in new cohorts, but 

the use of vaccines may differ between a country that has had large epidemics versus countries 

that have endemic disease. 

Noting that there is endemic dengue in Puerto Rico, Dr. Sun (FDA) asked whether in the 

epidemic curve for Zika the dengue cases could be superimposed with Zika cases in order to 

get a sense of whether Zika is declining is because the rainy season is over and there is less 

transmission of all types of mosquitos, or if it is just a case of Zika going away. 

Ms. Martin responded that it is probably a combination of multiple factors. They have had a 

large epidemic, and it is likely that the true burden has been underestimated. In addition, most 

of the island has now been affected, so the number of susceptibles has also probably dropped. 

She said she did not want to make any comments about the vector side because she is not an 

arboviral expert, but it is likely multi-factorial. 

Dr. Fryhofer (AMA/ACP) requested guidance on what to tell patients when they are traveling to 

areas like French Polynesia that do not have high levels of active infection right now, but 

certainly have had peaks in the past. 

Ms. Martin replied that CDC is currently considering its guidance for endemic areas. Obviously, 

pregnant women who are traveling to any areas that may have transmission of Zika should take 

precautions. 

Dr. Bennett reminded everyone that in February 2017, there will be a session on Zika vaccine to 

update ACIP on the state of the science. 

Agency Updates 

Centers for Disease Control and Prevention (CDC) 

Dr. Messonnier emphasized that CDC remains very occupied with the Zika response. Dr. 

Frieden always characterizes it as the most complicated response CDC has ever managed. 

This is partly due to the fact that so many parts of the agency are engaged, because it is so 

multifactorial and because the science continues to evolve. Regarding the use of vaccines, as 

always, CDC will call upon the ACIP for assistance in thinking about US vaccination policy. 

On September 29th, CDC and the National Foundation for Infectious Diseases (NFID) held a 

joint press conference to kick off the 2016-2017 Influenza Vaccination Campaign. For the 2016­

2017 season, vaccine manufacturers have estimated that up to 168 million doses of injectable 

influenza vaccine will be available. More than 93 million doses of influenza vaccine already 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

have been delivered. This season’s vaccines have been updated. Most of the research 

suggests that they will cover the strains that are more common during 2016-2017. As of this 

week, overall influenza activity was low in the continental US (CONUS). Adult influenza 

coverage was low last year, but CDC is working to try to understand that and figure out what to 

do to improve influenza coverage this year. 

The National Immunization Conference (NIC) was held in September in Atlanta, with thousands 

of immunization enthusiasts in attendance. It was actually the largest number of attendees NIC 

has ever had. She expressed gratitude for the many individuals and groups in the room for their 

strong support. The next National Adult and Influenza Immunization Summit (NAIIS) will be 

held in Atlanta in May 2017. 

In terms of the election, CDC is working with HHS and the Office of Management and Budget 

(OMB) to plan and prepare for any administrative changes to come. The processes will 

accelerate following the election. 

Globally, CDC is consistently reminded of the challenges to building global capacity for public 

health. Earlier this year, colleagues in CDC’s Global Immunization Division (GID) released 

CDC’s Strategic Framework for Global Immunization 2016-2020. The framework is built around 

five interconnected goals: an overarching goal to improve global health impacts; three goals to 

increase the amount of people reached by strengthening country-owned immunization 

programs; and CDC’s foundational goal of providing evidence for effective policy and program 

implementation. That framework is available on the CDC website. 

International collaboration will continue to be important as CDC looks to enhance new 

technologies, including for example learning about other countries that are continuing to use the 

nasal influenza vaccine this year. There is also much that can be learned about vaccine policy 

from CDC’s international partners. CDC is pleased to be able to welcome its partners from 

China who are here to discuss priority scientific activities, and is glad to have the opportunity to 

learn from each other. 

Centers for Medicare and Medicaid Services (CMS) 

CMS recently issued a Medicare Provider notice regarding Medicare payment for the 

quadrivalent influenza vaccine. This notice instructs Medicare Administrative Contractors to pay 

for this vaccine using code 90674 with no coinsurance and deductibles. Coverage of the 

quadrivalent influenza vaccine was effective August 1, 2016. Because claims processing 

changes will be implemented on January 1, 2017, contractors and providers have been told to 

hold the claims until after that date. 

Department of Defense (DoD) 

Dr. Deussing expressed DoD’s appreciation for the valuable work of ACIP and the opportunity 

to participate in this work, which helps protect this country’s service members, their families, and 

all 9.4 million DoD beneficiaries worldwide. He briefly highlighted two current vaccine issues for 

the DoD. First, the DoD is working with the manufacturer of IMVAMUNE®, the non-replicating 

smallpox vaccine, to fulfill the final Phase 3 study requirement for licensure. Complete 

enrollment is expected by December 2016. IMVAMUNE® is projected to meet the US 

government’s preparedness requirement for development of an attenuated smallpox vaccine in 

sufficient quantity to protect 66 million people, comprising those for whom replicating smallpox 

vaccine is contraindicated and their household contacts. Second, he reminded everyone that 

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the previous day they heard an excellent presentation on the current YF vaccine supply 

challenges. The DoD has worked very hard to mitigate the effects of the YF vaccine shortage 

through close collaboration with the Defense Logistics Agency (DLA), the military departments, 

other federal partners, and Sanofi Pasteur. As a result of this concerted effort, the DoD reduced 

utilization of YF vaccine by 80%, but still vaccinated all service members and beneficiaries 

deploying to or traveling to a YF endemic area. The DoD looks forward to the availability of the 

Expanded Access IND for STAMARIL®, and will continue to work with its partners on solutions 

to this shortage. 

Department of Veterans Affairs (DVA) 

Dr. Pittman reported that the VA is nearing completion for national release of its latest software 

patches as part of the Veterans Immunization Enhancement 2.0 Project. These patches 

improve support for upcoming user-facing enhancements in its EMR and the Enterprise Health 

Management Platform (eHMP). They also provide multidivisional support for the VA’s larger 

integrated facilities to track immunization inventory more closely. VA has partnered with 

Walgreen’s for the 2016-2017 influenza season and will receive data for veterans who obtain 

their immunizations at Walgreen’s during the influenza season. This information with then be 

available in the VA’s Veterans Information Systems and Technology Architecture (VistA) EHR in 

any facility where that veteran is registered. 

Food and Drug Administration (FDA) 

Dr. Sun reported that since the June 2016 ACIP meeting, FDA approved two additional 

seasonal influenza quadrivalent vaccines, Afluria® and Flublok®. In addition, FDA approved the 

use of Prevnar13® for ages 18 through 49 and the 9vHPV 2-dose regimen. In addition, 

recognizing the importance of LAIV for both seasonal and pandemic influenza, FDA has been 

working very closely with the manufacturer, representatives from the ACIP Influenza WG, and 

CDC on further evaluation of the root cause of the observation of lower effectiveness in the 

observational studies. This includes work on many fronts, including manufacturing issues, 

further analysis of observational data, and virologic studies. FDA will continue to work closely to 

address these problems. 

Health Resources and Services Administration (HRSA) 

Dr. Nair reported that the National Vaccine Injury Compensation Program (VICP) has had a very 

busy year processing claims for Fiscal Year 2016, for which 1116 claims were received. At the 

end of the Fiscal Year, the VICP awarded approximately $250 million that were paid to 

petitioners and attorneys for their fees for compensated and dismissed claims, as well as interim 

fees and costs. More information and data about this program can be found on HRSA’s 

website. HRSA is in the process of updating the Vaccine Injury Table. Comments on the 

Notice for Proposed Rulemaking proposing changes to the Vaccine Injury Table have been 

reviewed, and a draft Final Rule is being developed. It is currently going through the clearance 

process, and HRSA hopes to have that finalized and published in the Federal Registry before 

the end of this calendar year. As of August 2016, HRSA’s Countermeasures Injury 

Compensation Program (CICP) has compensated 39 claims totaling $4.9 million. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Indian Health Services (IHS) 

Dr. Groom reminded everyone that IHS developed a policy to require influenza vaccine for its 

HCP last season, but had not successfully bargained for it with the unions, so they were able to 

only partially implement it in IHS facilities. Even with only partial implementation, they achieved 

about a 10% increase and had coverage of approximately 85% for IHS HCP. She said she was 

very pleased to report that they completed bargaining with two of the largest unions, so 97% of 

IHS union employees are now covered by this policy, which they expect to implement fully 

across the IHS. They are hopeful that they might achieve the Healthy People 2020 goal this 

season. IHS is pleased to join a number of private and public institutions on the IAC’s honor roll 

and have their federal mandate there along with the DoD colleagues. Regarding maternal 

immunizations, IHS is partnering with Johns Hopkins to develop a performance measure for the 

IHS to assess influenza and Tdap vaccination among pregnant women, and a reminder in the 

IHS EHR for its providers. 

National Institutes of Health (NIH) 

Dr. Gorman reported that with regard to revision of the Common Rule, the comment period is 

now closed. Approximately 1500 public comments were received during the comment period. 

Some comments contained over 150 signatures. The agencies involved are now reviewing 

these comments and making decisions on how to respond. The multiple agencies involved are 

presently driving toward consensus. They have heard that there may be an announcement 

soon. 

NIH is now requiring a single IRB for all clinical trials that include multiple sites. Policy 

Announcement NOT-OD-16-094: Final NIH Policy on the Use of a Single Institutional IRB for 

Multiple Site Studies was published on June 21, 2016. This policy describes the rational for this 

policy and exemption criteria during the transition period. 

In terms of personnel, NIH has two new institute Directors. The National Institute of Mental 

Health (NIMH) has appointed Dr. Joshua Gordon as its new Director: https://www.nih.gov/newsevents/news-releases/nih-names-dr-joshua-gordon-director-national-institute-mental-health 

The National Institute of Child Health and Development (NICHD) has appointed Dr. Diana 

Bianchi as its new Director: https://www.nih.gov/news-events/news-releases/nih-names-drdiana-bianchi-director-national-institute-child-health-human-development. 

In terms of the National Institute of Allergy and Infectious Diseases (NIAID), NIAID researchers 

in influenza have advanced the understanding of how influenza protection can facilitate the 

development of a universal or broadly protective influenza vaccine. A nanoparticle vaccine 

based on an H1N1 stem, rather than the HA head, offered protection against a lethal dose of 

H5N1 challenge. This protection was antibody based, but did not develop neutralizing titers, 

which will present an issue in terms of attempting to license the new vaccines: 

http://www.niaid.nih.gov/diseases-conditions/niaid-researchers-advance-development-universalflu-vaccine. 

In terms of personnel at NIAID, Dr. Stephen Holland was named the Director of the Division of 

Intramural Research (DIR): https://www.niaid.nih.gov/news-events/niaid-selects-directordivision-intramural-research. NIH continues to search for a new Division Director for Division of 

Microbiology and Infectious Diseases (DMID). Dr. Fred Cassels, Branch Chief of the Enteric 

and Hepatic Diseases Branch (EHDB) retired from government service on September 30, 2016. 

He will be continuing his career with a new position at PATH. 

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NIAID is working on a new YF vaccine. A phase 1 trial is underway for safety and 

immunogenicity: https://www.nih.gov/news-events/nih-launches-early-stage-yellow-fevervaccine-trial. While it will not answer Dr. Plotkin’s question about Lyme Disease vaccine, NIAID 

is in the early planning phases for a clinical trial to evaluate the effectiveness of prophylaxis of 

tick bites to prevent Lyme Disease. In terms of the Zika virus, NIAID is actively pursuing 

multiple vaccine candidates to prevent Zika virus infections, including the following strategies: 

 A DNA-based vaccine that uses a strategy similar to an investigational flavivirus vaccine for 

West Nile virus infection, which entered an early-stage trial in August 2016 and the dosing of 

those individuals is now complete 

 A live-attenuated investigational Zika vaccine building on a similar vaccine approach for the 

closely-related dengue virus 

 An investigational Zika vaccine that uses a genetically engineered version of vesicular 

stomatitis virus (VSV), with plans underway to evaluate this candidate in tissue culture and 

animal models 

 A whole-particle inactivated Zika vaccine based on a similar vaccine approach used by the 

Walter Reed Army Institute of Research (WRAIR) to develop vaccines against the related 

Japanese Encephalitis (JE) and dengue viruses; information regarding NIAID-supported 

Zika research may be found here: https://www.niaid.nih.gov/diseases-conditions/zika-virus 

NIH and Fundacao Oswaldo Cruz-Fiocruz (Fiocruz), a national scientific research organization 

linked to the Brazilian Ministry of Health, have begun a multi-country study to evaluate the 

magnitude of health risks that Zika virus infection poses to pregnant women and their 

developing fetuses and infants. The study is also opening in Puerto Rico and will expand to 

several locations in Brazil, Colombia, and other areas that are experiencing active local 

transmission of the virus. The Zika in Infants and Pregnancy (ZIP) study plans to enroll as 

many as 10,000 pregnant women ages 15 years and older at up to 15 sites. The participants 

will be in their first trimester of pregnancy and will be followed throughout their pregnancies to 

determine if they become infected with Zika virus and if so, what outcomes result for both 

mother and child. The participants’ infants will be carefully followed for at least one year after 

birth. Here is a link to the NIH press release from June 21, 2016: https://www.nih.gov/newsevents/news-releases/nih-launches-large-study-pregnant-women-areas-affected-zika-virus. 

Some suggested publications include: 

 Gonorrhea Vaccine: LM Wetzleret al. Summary and recommendations from the National 

Institute of Allergy and Infectious Diseases (NIAID) workshop "Gonorrhea Vaccines: the 

Way Forward."ClinVaccine Immunol(2016 Aug 5) 

 Zika Vaccines: Nature: Vaccine protection against Zika virus from Brazil, 

http://www.nature.com/nature/journal/v536/n7617/full/nature18952.html 

 Zika Vaccines: Science: Protective efficacy of multiple vaccine platforms against Zika virus 

challenge in rhesus monkeys, 

http://science.sciencemag.org/content/early/2016/08/03/science.aah6157 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

National Vaccine Program Office (NVPO) / NVAC 

Dr. Birkhead reported for both NVPO and NVAC. First, as a companion to the National Adult 

Immunization Plan (NAIP) released last February, NVPO plans to release a Pathway to 

Implementation of Adult Immunization Report in the near future to facilitate action on the goals 

of the original plan. The report suggests 8 priorities and potential activities to focus on, down 

from the 78 strategies in the original plan, and include: 

 Addressing technical and legal and administrative and practical barriers to greater use of 

EHRs and immunization registries to track adult immunization data 

 Evaluating the impact of current healthcare quality measures for adult vaccination and the 

feasibility of developing composite measures 

 Assessing the impact of financial barriers such as co-pays on adult vaccination uptake 

 Identifying legal, practical, and policy barriers impeding expansion of adult immunization 

 Encouraging all providers to implement the NVAC Standards for Adult Immunization 

Practice 

 Engaging community leaders in promoting the importance of adult vaccination to the public 

 Examining the total costs of adult vaccination to adult vaccine providers for providing 

vaccine services such as vaccine ordering, handling, storage, administration, patient recall 

and reminders, counseling, et cetera 

NVPO recently awarded two contracts that may be of interest. The first contract addresses the 

last point about the cost to providers of adult immunization by looking in detail at the business 

case for providers of adult immunizations, taking into account both the costs and the 

reimbursement by provider type and geographic region. The second contract is for the 

development and testing of a composite healthcare quality measure for maternal immunizations 

with the National Committee for Quality Assurance (NCQA), incorporating both Tdap and 

influenza vaccinations. This was referenced the previous day by Dr. Carol Hayes in the context 

of the Adult Vaccine Summit Quality Performance Measure WG led by LCDR Angela Shen at 

NVPO. 

NVPO and CDC are collaborating to put on a webinar entitled Vaccines During Pregnancy: A 

Strong Record of Safety to help providers address patient concerns around maternal 

immunization. The webinar will be on November 9th from 12:00 PM to 1:30 PM Eastern Time 

and will cover the effectiveness of influenza and Tdap vaccines in pregnant women, their safety 

profile and common mild AEs, a review of the vaccine safety surveillance efforts and research 

activities specific to maternal immunizations, and strategies and resources to address patient 

concerns around maternal immunizations. To view the webinar, register at the NVPO home 

page at hhs.gov/nvpo. 

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The last NVAC meeting was on September 20th and included presentations / discussions on 

CDC’s Strategic Framework for Global Immunization 2016-2020, the mid-course review of the 

2010 NVP, NVPO’s Pathway to Implementation of Adult Immunization Report, and a review of 

the process of developing healthcare quality measures. That discussion kicked off the process 

to develop consolidated quality measures, both for adult and maternal immunizations. During 

the meeting, NVAC also voted on and unanimously adopted a Maternal Immunization WG 

(MIWG) report called Overcoming Barriers and Identifying Opportunities for Developing 

Maternal Immunizations. That report is available on the NVPO website and will be published in 

Public Health Reports (PHR). The next NVAC meeting is February 7-8, 2017 at the Humphrey 

Building and will be available by webcast. 

 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Child and Adolescent Immunization Schedule 

Introduction 

Dr. José R Romero 

Chair, Child and Adolescent Immunization Work Group 

Dr. Romero introduced this session on behalf of Child and Adolescent Immunization Schedule 

WG. He reminded everyone that the schedule is presented for a vote every fall, given that the 

ACIP’s approval is necessary prior to publication of the schedule in the MMWR January or 

February of the following year. ACIP’s approval is also necessary before its partners the 

American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), and 

American Congress of Obstetricians and Gynecologists (ACOG) review and approve the 

schedule. He emphasized that no new policy is established by the schedule; rather, it reflects a 

summary of published ACIP recommendations. These edits are intended to improve readability 

and utility of the schedule, and hence translate the respective ACIP recommendations into 

language that is easy to use and interpret by busy practitioners. 

Dr. Romero indicated that for the remainder of this presentation, Dr. Robinson would discuss 

proposed edits to some specific vaccine footnotes as well as Figure 1, and would introduce a 

proposed child/adolescent high-risk figure which, if adopted, would become figure 3. This year, 

a few vaccines’ schedules required attention. ACIP members were provided with these slides in 

their binders, as well as on the meeting background materials’ website. The slides presented 

during this session were updated to include footnote and figure edits that incorporate the results 

of the previous day’s votes. The changes to the footnotes include edits to the HepB, Hib, 

pneumococcal, influenza, meningococcal, and HPV footnotes. 

Child and Adolescent Immunization Schedule 2015 

Candice L. Robinson, MD, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Robinson indicated that on the title page, the title was changed to “Recommended 

Immunization for Children Aged 18 Years or Younger.” This new title harmonizes with the new 

adult immunization title to be presented later in the morning. The year was updated to 2017. 

There are no proposed changes for Figure 2, the catch-up schedule. 

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In the 2016 version of the schedule, the text beneath Figure 1 was largely a repeat of the text 

that already appeared on the title page of the schedule. In the proposed 2017 version, this text 

has been removed. There are a number of proposed additions to Figure 1 for the 2017 

schedule. The age 16 years has been separated from the ages 17 through 18 years, and the 

16-year column has been shaded. The WG felt that this change would highlight the need for the 

meningococcal conjugate vaccine booster dose at this age. This also may provide an 

opportunity for catch-up vaccination if other adolescent vaccinations have not yet been 

administered or the series has not yet been completed. 

Within the influenza row, live attenuated influenza vaccine (LAIV) has been removed as a 

recommended vaccine given the ACIP recommendation to not use LAIV during the 2016-2017 

influenza season. Last year, a purple bar was added within the HPV row at age 9 through 10 

years to represent the recommendation to begin the HPV series at age 9 years in children with 

a history of sexual abuse or assault. Feedback was received from providers who indicated that 

this bar did not reflect the recommendation that HPV may be started at 9 years of age for those 

without a history of sexual abuse or assault. A blue bar was added at age 9 to 10 years to 

indicate that vaccination may begin at 9 years of age, even if there is no history of sexual abuse 

or assault. Here is the revised schedule: 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

The proposed high-risk figure pictured below demonstrates that most children with medical 

conditions can, and should, be vaccinated according to the routine child/adolescent 

immunization schedule. It indicates when a medical condition is a precaution or contraindication 

to vaccination. It also indicates when additional doses of vaccines may be necessary 

secondary to the child’s/adolescent’s medical condition: 

On the high-risk figure, the yellow color indicates “Vaccination according to the routine schedule 

recommended.” The purple color indicates “Recommended for persons with an additional risk 

factor for which the vaccine would be indicated.” The black and yellow stippled pattern indicates 

“Vaccination is recommended and additional doses may be necessary based on medical 

conditions. See footnotes.” The white color indicates “No recommendation.” The red indicates 

vaccination is “Contraindicated.” The orange color indicates “Precaution for vaccination.” 

Within the Additional Information section of the footnotes, providers are referred to the ACIP 

general recommendations on immunization and the relevant vaccine specific ACIP statement 

for additional contraindications and precautions information. The following additional changes 

were made to the footnotes: 

 A bullet was added on the National VICP. This addition was made to harmonize with the 

adult schedule, which already contains information regarding the program and the vaccines 

covered. 

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 The HepB footnote was updated to reflect the recommendation for HepB administration 

within 24 hours of birth. For infants born to HBsAg-positive mothers, the post-vaccination 

testing window was updated to reflect the new recommendation of testing at age 9 through 

12 months. 

 Within the Haemophilus influenzae type B (Hib) footnotes, HIBERIX® was added to the list of 

vaccines that may be administered for the primary Hib series. Additionally, COMVAXTM was 

removed from the list of available vaccines, as this vaccine is no longer produced and all 

doses of the vaccine have now expired. Language regarding the restricted use of HIBERIX® 

has been removed. The Catch-Up Vaccination section has been clarified to reflect that 

unvaccinated children 15 through 59 months of age should receive 1 dose of Hib vaccine. 

 Throughout the pneumococcal footnotes, mention of PCV7 vaccine has been removed as 

the last doses of PCV7 vaccine expired in 2010. Thus, children who received PCV7 as part 

of a primary pneumococcal series have since aged out of the routine pneumococcal 

recommendation. 

 Within the influenza footnotes, information regarding LAIV has been removed and the 

following statement has been added, “For the 2016-17 season, use of live attenuated 

influenza vaccine (LAIV) is not recommended.” The MMWR reference has been updated to 

reflect the 2016-2017 influenza recommendations publication. 

 In the meningococcal footnotes, the Clinical Discretion section outlines the MenB category B 

recommendations. This section has been updated to read, “Young adults aged 16 through 

23 years (preferred age range is 16 through 18 years) may be vaccinated with a 2-dose 

series of either Bexsero® (0, ≥1 month) or Trumenba® (0, 6 months) vaccine to provide shortterm protection against most strains of serogroup B meningococcal disease.” This reflects 

the recommendations made during the previous day’s vote. Within the Meningococcal 

Conjugate Vaccine section, children with HIV infection have been added to the section 

regarding vaccination of persons with high-risk conditions. The footnote regarding use of 

MenB among persons with high-risk conditions will remain unchanged, recommending a 2­

dose series of Bexsero® at least 1 month apart, or a 3-dose series of Trumenba® with the 

second dose at least 1-2 months after the first and the third dose at least 6 months after the 

first dose. The reference and website for the meningococcal and HIV-infected persons 

MMWR will be added once the citation is available. 

 Within the Tdap footnote, language was added regarding vaccination among pregnant 

women. The footnote states, “Administer 1 dose of Tdap vaccine to pregnant adolescents 

during each pregnancy, preferably early during gestational weeks 27 through 36 weeks 

gestation, regardless of the time since prior Td or Tdap vaccination.” Additionally, the 

Catch-Up Vaccination section has been updated to indicate that persons who receive a 

dose of Tdap at age 7 through 10 years as part of a catch-up series, may receive a Tdap at 

11 through 12 years of age. 

 The HPV footnote was re-written to reflect the recommendations approved during the 

previous day’s vote. Routine vaccination now reads, “Administer a 2-dose series of HPV 

vaccine on a schedule of 0, 6-12 months to all adolescents aged 11 or 12 years. The 

vaccination series can start at age 9 years. Administer HPV vaccine to all adolescents 

through age 18 years who were not previously adequately vaccinated. The number of 

recommended doses is based on age at administration of the first dose. For persons 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

initiating vaccination before age 15, the recommended immunization schedule is 2 doses of 

HPV vaccine at 0, 6-12 months. For persons initiating vaccination at age 15 years or older, 

the recommended immunization schedule is 3 doses of HPV vaccine at 0, 1–2, 6 months. A 

vaccine dose administered at a shorter interval should be re-administered at the 

recommended interval.” For special populations the language reads, “For children with a 

history of sexual abuse or assault, administer HPV vaccine beginning at age 9 years. 

Immunocompromised persons* including those with human immunodeficiency virus (HIV) 

infection, should receive a 3-dose series at 0, 1–2, and 6 months regardless of age at 

vaccine initiation. Note: HPV vaccination is not recommended during pregnancy, although 

there is no evidence that the vaccine poses harm. If a woman is found to be pregnant after 

initiating the vaccination series, no intervention is needed; the remaining vaccine doses 

should be delayed until after the pregnancy. Pregnancy testing is not needed before HPV 

vaccination.” 

In conclusion, Dr. Robinson posed the following questions for discussion: 

 Does ACIP approve of the edits to the pre-existing portions of the child/adolescent 

schedule? 

 Does ACIP approve of the proposed high-risk figure for inclusion in the 2017 schedule? 

Discussion Points 

Dr. Bennett requested that the discussion be limited to conceptual issues, and that any edits to 

the wording be submitted to Dr. Robinson to be taken into consideration. 

As a primary care pediatrician, Dr. Szilagyi said he thought the high risk figure could be 

incredibly helpful. The next burden will be on partner organizations, AAP and AAFP, for how to 

translate that into very practical methods such as prompts or alerts in the EMR or codes so that 

high risk patients can be flagged. 

Dr. Moore agreed that the high risk figure would be very helpful for those caring for children. 

Focusing on the two vaccines being used now that have a 2-dose or 3-dose schedule, MenBFHbp and HPV vaccine, she requested that someone look carefully at the math on 

recommended intervals. For example, if someone is using a 2-dose schedule and gives the 

dose too early at less than 6 months, the recommendation for MenB-FHbp is if it is 0 and less 

than 6 months, repeat the dose 6 months later. That actually is much longer than the interval 

that could be used for an ordinary 3-dose schedule of that vaccine, which is 0, 1-2, and 6 

months. This issue is also true for the HPV vaccine. She emphasized that a minimum schedule 

for administration of 3 doses should not vary based on one’s intention to try a 2-dose schedule 

versus a 3-dose schedule. There should just be one minimum schedule regardless of what is 

intended for those 3 doses. Operationally, that is really important. She said she would feel silly 

telling someone they would have to wait longer than they would if they were using a 3-dose 

schedule. 

Dr. Robinson replied that the Policy Note for HPV vaccine has some draft language about what 

to do if a dose is administered early in a 2-dose schedule versus administering a dose early in a 

3-dose schedule. Portions of that Policy Note draft can be added to make it clear to providers 

what to do based on what schedule they were attempting initially. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Cohn added that they could speak with the SMEs for those two vaccines as well to ensure 

that the Policy Notes math is right as well. 

Dr. Middleman (SAHM) expressed gratitude for the great schedules. She pointed out that the 

title still uses the word “children” instead of “persons.” All of the figures state “persons.” From a 

developmental perspective in terms of what constitutes a child, adolescent, or adult, those are 

developmental terms. The preference would be to use ages, because they do not talk about a 

toddler schedule. It is a developmental stage. SAHM appreciates the highlighting of places in 

the schedule with 4-6, 11-12, and 16 where there is a new place to have a vaccine. 

Dr. Robinsons said they could change it to “persons” or “children and adolescents.” She 

thought they did this because the other schedule uses “adults.” 

Dr. Belongia expressed gratitude for a really great figure for practitioners. He asked about any 

plans for translating this for clinical decision support systems, which will become increasingly 

important going forward, and development of rules to translate these categories into analytical 

quantitative measures. 

Dr. Wharton responded that the challenges of translating the ACIP recommendations into 

clinical decision support is something CDC recognizes as well and is continuing to think about 

how to incorporate this into WG work. This cannot be undertaken within the schedule process. 

It needs to be addressed with individual recommendations. CDC is open to suggestions for how 

to proceed with that. This is an ongoing challenge that they are trying to take on. 

Dr. Kempe said she knew of a number of different systems that already have done this. She 

suggested beginning with people who have already done this to avoid duplication. 

Dr. Lee said that she loved the figures. She recalled that the previous day, there was 

discussion about standardizing terminology or perhaps providing examples of what constitutes 

CLD. Similarly, this should be done for all of the categories. Some of them are very binary and 

others are more challenging. For example, “level of immunocompromise” is difficult to assess. 

It might be helpful to offer categories of guidance, depending on the level of 

immunocompromise. 

Dr. Cohn indicated that there are plans to address this issue over the next year more completely 

throughout all of the language and recommendations. Making sure these schedules are clear 

can be included in that process. 

Vote: Child and Adolescent Immunization Schedule 

Dr. Belongia made a motion to approve the Child and Adolescent Immunization Schedule and 

the High-Risk Figure. Dr. Kempe seconded the motion. The motion carried with 14 affirmative 

votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as follows: 

14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

0 Opposed: N/A 

0 Abstained: N/A 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Adult Immunization Schedule 

Introduction 

Laura E. Riley, MD 

Chair, Adult Immunization Work Group 

Advisory Committee on Immunization Practices 

Dr. Riley began by thanking Dr. Kathleen Harriman for her leadership as Chair of the Adult 

Immunization WG for many years, recognizing her remarkable ability to cut through the forest of 

footnotes and succinctly get them to where they needed to be. She will remain on the WG as a 

consultant. She also welcomed new member Dr. Paul Hunter, who brings his public health and 

clinical perspective to the WG. 

She reminded everyone that ACIP updates the adult immunization schedule each year. The 

schedule represents current ACIP policy and also updates approved policy changes from ACIP 

meetings. The Adult Immunization WG meets monthly and engages in ongoing consultation 

with vaccine SMEs to recognize changes over time. Updates in the adult immunization 

schedule are approved by the following: 

 American College of Physicians (ACP) 

 American Academy of Family Physicians (AAFP) 

 American Congress of Obstetricians and Gynecologists (ACOG) 

 American College of Nurse Midwives (ACNM) 

The adult immunization schedule is published in the MMWR and the Annals of Internal 

Medicine. 

There will be several updates to the schedule, which are derived from the ACIP 

recommendations and include the following: 

 Influenza vaccination (June 2016) 

 Do not use LAIV in 2016–2017, modified language on egg allergy 

 Tdap vaccination (October 2016) 

 Guidance for use during pregnancy 

 HPV vaccination (October 2016) 

 Updated dosing schedule 

 Hepatitis B vaccination (October 2016) 

 Updated at risk populations 

 Meningococcal vaccination (June and October 2016) 

 Use MenACWY vaccine for adults with HIV, updated schedule for MenB-FHbp 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

 Format changes 

Recommended Immunization Schedule for Adults Aged 19 Years or Older, United 

States, 2017 

Unified cover page, figures, footnotes, table – 6 panels 

Considered human factors and ergonomics for figures 

Modified footnotes for simplicity and consistency 

Adult Immunization Schedule 

Dr. David Kim 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

In this presentation, Dr. Kim described the proposed changes to the 2017 Adult Immunization 

Schedule. The 2017 schedule is now a 6-panel document with a cover page of introduction and 

general information, two figures with accompanying footnotes, and a table of contraindications 

and precautions. 

On the updated cover page, the title has been changed to “Recommended Immunization 

Schedule for Adults Aged 19 Years or Older, United States, 2017.” It is now consistent with the 

Child and Adolescent Schedule. The text that was in the periphery of Figures 1 and 2 in the 

2016 schedule has been moved to the cover page. The revised cover page introduces a list of 

acronyms used for vaccines routinely recommended for adults. When these changes are 

incorporated, the cover page for the proposed 2017 schedule contains more information and 

looks like this: 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

The changes proposed for Figure 1 for 2017 include the following: 

 Revise the title and instruction to the reader 

 Combine age groups 27 through 49 and 50 through 59 to create the new age group 27 

through 59 

 Use the acronyms introduced in the cover page in the vaccine column 

 Lump the live vaccines (MMR, varicella, zoster) together to consolidate information and to 

simplify graphics 

 Use colored blocks instead of colored bars for indication 

 Move the footnote on the VICP to the cover page 

 Remove the clause “zoster vaccine is recommended regardless of past episode of zoster” in 

the legend, because the information is contained in the footnote for zoster vaccination 

 Move the text to the cover page. 

After incorporating the proposed changes, this is what the proposed Figure 1 would look like: 

The changes proposed for Figure 2 for 2017 include the following: 

 Make the changes already described for Figure 1 

 Move the column for MSM to the right of healthcare personnel to lump at-risk populations 

 Update the footnotes to link them with the information specified by medical conditions and 

other indications 

 To reflect the recommendation made by ACIP in June to routinely vaccinate adults with HIV 

infection with serogroups A, C, W, and Y meningococcal vaccine, change the color of this 

indication bar for this group from purple to yellow 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

After incorporating the proposed changes, this is what the proposed Figure 2 would look like: 

Proposed changes to the Table of Contraindications and Precautions include the following: 

 Add general information to explain the significance of contraindications and precautions for 

vaccination 

 As in Figures 1 and 2, use acronyms for the vaccine column and list the acronyms at the 

bottom of the new page 

 Consolidate contraindications and precautions that are applicable to all routinely 

recommended vaccines 

 List additional contraindications and precautions for applicable vaccines 

 Revise precaution for IIV in egg allergy per June 2016 update 

 State that LAIV should not be used during the 2016-2017 influenza season 

Currently, this table is available through the ACIP website and is a standalone document that is 

not integrated into the schedule. However, it will become a part of the schedule in 2017. Here 

is what the Table of Contraindications and Precautions will look like based on these changes: 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

The footnotes went through a substantial makeover. The proposed footnote revisions for 

Figures 1 and 2 include the following: 

 The footnotes are limited to information about vaccines: 

 The footnote on General information was moved to the cover page 

 The footnote on Immunocompromising conditions was removed, with applicable 

information added to specific vaccination sections 

 To standardize the structure, each footnote has been formatted to include the following: 

 A general information section that describes routine recommendations 

 A special populations section that describes recommendations for groups identified 

in Figure 2 

 To standardize the content, each footnote has been reviewed and revised to ensure the 

following: 

 Consistent sentence structure, flow of information, use of mathematical symbols and 

acronyms 

 Trade names are included for identification purposes only (hepatitis B and 

meningococcal vaccines) 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Changes to the content of specific footnotes follow, with the changes shown as strikethroughs 

(deletions) and / or underlines (additions): 

Footnote 1. Influenza Vaccination 

 General information 

All persons aged 6 months or older... 

Adults aged 65 years or older may receive high-dose IIV or adjuvanted IIV 

Healthcare personnel who care for severely immunocompromised persons... should 

receive IIV or RIV; [those] who receive LAIV should avoid providing care for severely 

immunocompromised... 

LAIV should not be used during the 2016–2017 influenza season 

 Special populations 

Adults with a history of egg allergy who have only hives after exposure to egg should 

receive age-appropriate IIV or RIV 

Adults with history of egg allergy other than hives may receive age-appropriate IIV or 

RIV. IIV should be administered in... medical setting and supervised by a healthcare 

provider... 

Pregnant women and women who might become pregnant in the upcoming influenza 

season should receive IIV 

Footnote 2. Td/Tdap Vaccination 

 General information 

Adults who have not received Tdap or for whom pertussis vaccination status is 

unknown should receive 1 dose of Tdap followed by a Td booster dose every 10 

years 

 Special populations 

Pregnant women should receive 1 dose of Tdap during each pregnancy, preferably 

early during gestational weeks 27–36, regardless of her prior history of receiving 

Tdap 

Footnote 4. Varicella Vaccination 

 General information 

Adults without evidence of immunity to varicella should receive... 

 Special populations 

Pregnant women should be assessed for evidence of varicella immunity... Birth 

before 1980 is not considered evidence of immunity 

Healthcare institutions should assess and ensure that all healthcare personnel have 

evidence of immunity to varicella. Birth before 1980 is not considered evidence of 

immunity... 

Adults with a malignant condition, including those affecting the bone marrow or 

lymphatic system, or systemic immunosuppressive therapy should not receive 

varicella vaccine 

Adults with HIV infection and CD4+ count ≥200 may be considered for a 2-dose 

series of varicella vaccine... CD4+ count <200 should not receive varicella vaccine 

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Footnote 5. Zoster Vaccination 

 General information 

Adults aged 60 years or older should receive 1 dose of zoster vaccine, regardless of 

whether they had a prior episode of herpes zoster 

Although... licensed by the U.S. Food and Drug Administration for... persons aged 

≥50 years... ACIP recommends... begin at age 60 years 

 Special populations 

Adults aged 60 years or older with chronic medical conditions may be vaccinated 

unless they have a medical contraindication... 

Adults with a malignant condition affecting the bone marrow or lymphatic system or 

who receive systemic immunosuppressive therapy should not receive zoster vaccine 

Adults with HIV infection and CD4+ count ≥200 have no zoster vaccine 

recommendation because there is a lack of evidence available for or against zoster 

vaccination... CD4+ count <200 should not receive zoster vaccine 

Footnote 6. HPV Vaccination 

 General information 

Adult females through age 26 years and adult males through age 21 years who have 

not received any HPV should receive a 3-dose series of HPV at 0, 1-2 and 6 months. 

Males aged 22 through 26 years may be vaccinated 

Adult females through age 26 years and adult males through age 21 years (and 

males aged 22 through 26 years) who initiated HPV series before age 15 years and 

received 2 doses at least 5 months apart are considered adequately vaccinated and 

do not need an additional dose of HPV 

Adult females and males... who initiated HPV series before age 15 years and 

received 1 dose or 2 doses at least 5 months apart are not... adequately 

vaccinated... and should receive 1 additional dose of HPV 

Note: HPV is routinely recommended... at age 11 or 12 years. For adults who 

initiated but did not complete HPV series, consider their age at first HPV vaccination 

and other factors to determine... adequately vaccinated 

 Special populations 

MSM through age 26 years, if not previously vaccinated, should... 

Adults through age 26 years with immunocompromising conditions (described 

below), including HIV, should receive... 

Pregnant women are not recommended to receive HPV... 

Footnote 9. Hepatitis B Vaccination 

 General information 

Adults who seek protection from HBV infection may receive a 3-dose series of... 

hepatitis B vaccine at 0, 1, and 6 months 

 Special populations 

Adults with chronic liver disease, hepatitis C virus infection, HIV infection, age <60 

years with diabetes... should receive... 

Adult patients receiving hemodialysis or with other immunocompromosing conditions 

should receive a 3-dose series of 40 mcg/mL Recombivax HB at 0, 1, and 6 months 

or a 4-dose series of 40 mcg/mL Engerix-B at 0, 1, 2, and 6 months 

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–	 

–	 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Footnote 10. Meningococcal Vaccination 

As a reminder, the ACIP recommendations made October 19, 2016 were: 

• For persons at increased risk and for use during outbreaks, 3 doses of MenB-FHbp 

should be administered at 0, 1–2, and 6 months 

• For healthy adolescents who are not at increased risk for meningococcal disease, 2 

doses of MenB-FHbp should be administered at 0 and 6 months 

• If second dose is given at an interval less than 6 months, a third dose should be given 

at least 6 months after the first dose 

This footnote reflects these recommendations and the recommendation made during the 

June 2016 meeting that persons with HIV should receive MenACWY as shown below. 

 Special populations 

Adults with... asplenia or... complement component deficiencies should receive... 

MenACWY... and either a 2-dose series of MenB-4C at least 1 month apart or a 3­

dose series of MenB-FHbp administered at 0, 1–2, and 6 months 

Adults with HIV infection... should receive a 2-dose primary series of MenACWY at 

least 2 months apart... Revaccinate with MenACWY every 5 years... MenB for 

adults with HIV infection is not routinely indicated... 

Microbiologists... should receive... MenACWY... and either a 2-dose series of 

MenB-4C... or a 3-dose series of MenB-FHbp... 

Adults at risk because of... outbreak... should receive... either a 2-dose series of 

MenB-4C... or a 3-dose series of MenB-FHbp... if the outbreak is attributable to 

serogroup B 

Young adults aged 16 through 23 years may be vaccinated with either a 2-dose 

series of MenB-4C at least 1 month apart or 2-dose series MenB-FHbp at 0 and 6 

months... 

When incorporated, the footnotes in the 2017 schedule would look like this: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Based on ACIP comments and suggestions during this session, the draft 2017 adult 

immunization schedule will be revised and reviewed again by the WG and SMEs. Concurrence 

will then be obtained by the ACP, AAFP, ACOG, and ACNM. The revised adult immunization 

schedule, including figures and footnotes, will be submitted to CDC for clearance by January 

2017. The cleared adult immunization schedule will be submitted to the MMWR as a Notice to 

the Reader referring the reader to the CDC website to access the updated schedule, and the 

Annals of Internal Medicine for publication in February 2017. With help from its partners, CDC 

will work to disseminate the schedule widely to help promote adult immunization. 

The 2017 Adult Immunization Schedule has gone through a lot of changes. The graphics were 

evaluated for usability and simplicity, the text in footnotes and elsewhere were overhauled for 

readability, completeness, and consistency. However, there is more work to do to improve the 

schedule as a useful tool for healthcare providers. Toward that end, CDC will kick off the Adult 

Immunization Schedule Evaluation Project in November 2016. Over the next year, CDC will 

conduct in-depth interviews of healthcare providers who use the adult immunization schedule to 

learn what their needs are, continue the efforts to improve the graphics and content of the 

schedule, and continue to work on improving the implementation of ACIP recommendations for 

immunizing adults. 

Discussion Points 

Dr. Messonnier explained that typically the schedule has been presented on the first day of the 

ACIP meeting. However, there would then be votes that impacted the schedule. This seemed 

out of order, so the decision was made to purposely change the schedule presentation to the 

second day of this meeting. She thanked Dr. Kim for incorporating all of the changes from the 

first day, and apologized for the copies provided to the members with incredibly small font. She 

assured everyone that they would keep working to give the members better access to ensure 

that they have adequate time to think about substantive changes. 

Dr. Bennett requested that everyone focus on the content versus the wording, given that there 

will be additional time to submit comments to Dr. Kim and his team to have some impact on the 

wording. 

Dr. Kempe said she thought they had done an incredibly good job of simplifying the schedule 

and that it was a great improvement. While the footnotes are still voluminous, she found them 

to be very well-organized. 

Dr. Lee said she liked having the presentation on the second day and thought the schedule was 

great. In many ways, it reinforced the intent of the recommendations, which came across in the 

wording of the schedule. Regarding the zoster vaccine, she wondered whether it should be 

distinguished that it was referring to the live attenuated vaccine because that will need to be 

clarified now or later as things change over time. Regarding immunocompromised individuals, 

the 3 doses of Hib post-stem cell transplant stood out to her, in part because stem cell 

transplants also are done in young children. That one recommendation seemed out of place to 

her, in part because she was trying to make it concordant with persons 18 years of age and 

younger, and she was trying to figure out why not the other vaccines that also would be 

administered. She suggested that additional thought be given to that detail. 

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Dr. Kim said that as a general reference, the Adult Immunization Schedule and the Child / 

Adolescent Immunization Schedule reflect decisions already made by ACIP and approved for 

publication. The inclusion of select vaccines, such as Hib, is because there are indications for 

that vaccine for adults. However, there are exceptions to routine recommendations. It is these 

exceptions that drive the volume up on in the footnotes. Where possible, the work group tried to 

minimize outlining all details but it’s a balancing act to have enough detail but not drive up the 

volume of the footnotes. The goal is to be as comprehensive as possible based on the 

recommendations already made by ACIP. 

Dr. Cohn added that as part of what they are talking about in terms of making some of these 

definitions consistent throughout the different vaccines over the next year, they also intend to 

find inconsistencies in the recommendations, but it may just be a different WG proposing 

different things. The goal is to harmonize in places where it seems reasonable. 

Dr. Fryhofer (AMA/ACP) did not think that the blocks instead of bars were practical. If looking at 

Figure 2 when trying to pick one of the special conditions and follow it down, it is not clear what 

goes with what. It would be a lot more practical for the busy practicing physician to be able to 

follow the headings down and figure out what immunizations that particular patient needs. 

Regarding Footnote 9: Hepatitis B Vaccination, she could not tell from what was shown on the 

screen if fatty liver disease was included specifically because this is being seen so much in 

practices and might not be a condition that many clinicians realize is an indication for hepatitis B 

vaccine. 

Referring to Figure 2, the high-risk figure in the pediatric schedule, with lines behind it, Dr. 

Messonnier asked whether that would solve the issue. 

Dr. Fryhofer (AMA/ACP) said that she had specifically compared the two and it would be very 

helpful. 

While she appreciated Figure 2 and the effort to address high-risk, Dr. Groom (IHS) expressed 

concern about how it will be interpreted. For example, looking down the list for MSM, it appears 

that MSM should receive PCV13 and PPSV23. For those who do not know that this is just for a 

certain medical indication, but not that medical indication, clinicians will look at it and think 

PCV13 must be given to all of their diabetic patients. Perhaps the footnote could be changed to 

state “may be recommended for patients with the appropriate medical condition,” but this is a 

high risk table and when people see that condition, she is afraid they will assume if it is purple, it 

means that a high-risk person should get it because they are in that special risk group. 

Dr. Thompson (NVAC) applauded the efforts to further develop this table and thought it was a 

big step forward. She noted that the tables for the younger individuals under 18 years of age 

did not include an MSM column. There also are some differences between the two tables in the 

pregnancy columns, which appear in both. Tdap is recommended for each pregnancy, so it is 

probably unusual that there are many individuals who have pregnancies under the age of 18. 

But, she wondered what the recommendation would be in that case in terms of the clinician 

reconciling these two things. Adolescents are “falling through the cracks” still, so reconciling 

these might be useful. Also, it was not clear to her why the vaccines were listed in the order 

that they were. It seemed to her that they could be listed alphabetically or at least in the same 

order on both charts. 

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Regarding the footnote under influenza pertaining to pregnant women and women who are 

planning to become pregnant during the upcoming influenza season, Dr. Wayne Hachey 

(Protein Science) suggested adding recombinant influenza vaccine (RIV) as it does have a 

Class B category for pregnancy and does not contain extras in the vaccine that many pregnant 

women avoid. He also suggested adding RIV for adults 65 years of age or greater. Protein 

Science submitted data to the WG and ACIP showing that Flublok® had increased effectiveness 

in the over 50 population to include the over 65 population during the influenza season. Even 

with the mismatch, Flublok® still provided protection for the over 65 group. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Regarding the exclusion of MSM on the child / adolescent schedule, Dr. Robinson pointed out 

that though vaccines for adults differ by MSM status, they do not differ for children. For 

instance, adult males 22 through 26 years of age receive HPV if they are MSM. However, all 

adolescents through 18 years of age are recommended to receive HPV vaccine. 

Regarding the order of vaccines presented for Figures 1 and 2, Dr. Kim indicated that these 

were done with graphics in mind. In years past, an effort was made to use alphabetical order 

but that simply did not work because of the complexity that it imposed on the eyes to follow. 

Other attempts were made with different colors, different shades, and hatching of the bars. 

However, through trial and error, the current listing was made. He invited recommendations to 

improve on that. 

Dr. Romero indicated that the ordering for the childhood / adolescent vaccines was an attempt 

to reflect how these vaccines are used and the timing in which they are used. There was 

discussion about putting them in alphabetical order, but it made more sense to the WG to leave 

them in the order in which they are introduced in children. 

Dr. Kempe wondered whether one of the concerns might be addressed by using the same 

wording for the purple color on the childhood schedule that basically states that one has to have 

an additional risk factor for which the vaccine would be recommended, or using the hatch 

marks. Those two wordings were created because of the concern raised that it was difficult to 

tell whether something was indicated or additional doses were needed. 

Dr. Messonnier expressed appreciation for all of the comments. One issue is that it is unknown 

how the schedule is used, especially by adult providers. It is clear that Pediatricians are using it 

routinely as part of their normal practice, and that the schedule has been vetted a lot. The issue 

of the adult schedule and extensive footnotes is that this is the first step toward moving the adult 

schedule. The questions everyone was asking were the same as the ones CDC is asking and 

hopes to get at through the testing of the schedule with adults, and asking how many clinicians 

use the schedule versus clinical support tools or online aids versus a hard, flat copy of the 

schedule on the wall. More information will be provided about this over the next year. They do 

not want to make dramatic changes until more information is acquired. 

Dr. Bennett replied that the goal was to ensure that the recommendations on the schedule 

match the influenza recommendations. 

Regarding the issue of how schedules are used in clinical practice, Dr. Hunter said that as a 

clinician and a public health practitioner, he did not think they were talking about the audience 

who administers vaccination, which is medical assistants and nurses. He suggested including 

their impressions of how the schedules are being used. Forecasts are printed out from 

registries or the EHR for a particular patient, but his impression is that clinicians look at the 

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schedule to double-check it to determine whether it really makes sense and then look at 

standing orders to determine whether to give the vaccination. 

Dr. Hayes (ACNM) registered her objection to using the word “lifestyle” as she does not think it 

is clinically appropriate. She agreed with Dr. Kempe about using the language for the purple 

bar from the child / adolescent schedule. 

Dr. Kim said he was hesitant to comment on that because it was not a decision made by him. It 

was a reflection of the content of previous publications on ACIP policy. ACIP could address 

that, as could the community that deals with these issues in general. 

Dr. Moore echoed the encouragement that if it is feasible at all, to use exactly the same wording 

on the purple bar for both adults and children in order to clean up the question about lifestyle. If 

using the same color, people who treat children and adults will anticipate that when they see the 

same color, it means exactly the same thing. 

Dr. Messonnier replied that they would review this to determine whether there is a way to make 

the language more harmonious with the childhood schedule and avoid pitfalls wherever 

possible. 

Dr. Fryhofer (AMA/ACP) said she thought internists are having to grapple with the increased 

complexity of adult immunization. They must learn from their pediatric colleagues and become 

more disciplined in looking at the adult schedule. It is totally different from the training many 

clinicians received in training during residency. It is a wonderful fact of life that there are now 

wonderful ways to keep people healthy, so the ACP has many efforts underway to help increase 

internists’ knowledge and use of the schedule. It is a very valuable tool. She expressed great 

appreciation for all of the work that the WG has put into making the schedule a “go to” source. 

She also expressed support for changing Figure 2 back to bars. 

Dr. Moore suggested that a nice way to deal with 2-dose versus 3-dose based on feedback from 

her colleagues who work in registry programming is simply for vaccines that may be given on a 

2- or 3-dose schedule to state “if the minimum interval for a 2-dose schedule is not met, please 

complete using the 3-dose schedule.” This avoids dealing with all of the convoluted language 

about invalid doses. 

Dr. Savoy (AAFP) emphasized that the schedules were simply summarizing what had already 

been decided and voted upon in the actual recommendations, so they could not just make 

changes as they pleased. For example, the term “lifestyle” must have been used in a 

recommendation so they could not just edit it in the schedule. She thought they probably would 

have to find the source recommendation and bring it before the committee for review. While 

family physicians have been relatively easy to train on the schedule because they see all ages, 

she is finding that a number of people are using electronic ways of managing the schedule. 

Although most everyone’s office has the schedule posted on the wall, the vast majority of 

people are getting their information from some type of electronic version. For example, the 

schedule has been translated into a variety of apps that people are using. Others are using it 

directly out of their EMR or their registry for their state pulls and sends them that information. 

Even though they spend a lot of time on how to make the schedule look pretty or how to make it 

work, she honestly did not think the vast majority of clinicians are spending as much time 

looking directly at the child or adult schedule as they are the content of what is behind it. She 

would be more interested in ACIP being crystal clear about the definitions of what they want and 

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14 Favored: Atmar, Belongia, Bennett, Ezeanolue, Hunter, Kempe, Lee, Moore, Pellegrini, 

Riley, Romero, Stephens, Szilagyi, Walter 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

the start and end points so that the registries are as accurate as possible, than worrying as 

much about the lines. 

Dr. Pittman (DVA) said that DVA eagerly awaits the release of the adult schedule every year, 

and asks Dr. Kroger to hold a webinar for the people in the field to discuss the changes, and it is 

very well-received. They do use the schedule to translate into an electronic record, because it 

is growing increasingly complex. 

Regarding the comment about influenza vaccine, Dr. Belongia thought it was a valid point that 

since ACIP does not make any preferential recommendations for any particular product, the 

language should state “use any licensed influenza vaccine” or it should list all of them. 

Ms. Stinchfield (NAPNAP) underscored the earlier comment about the end users of the 

schedules, the MAs and RNs. Their schedule WG takes that into consideration and talks about 

it quite a bit. CDC sent a team to Children’s Minnesota clinics to conduct focus groups, 

speaking to most of their MAs. The agency has done this across the country, and it is a really 

important point to keep focused on. 

Dr. Fryhofer (AMA/ACP) added the importance of eventually establishing a national 

immunization registry. Because the adult schedule has become so complicated, it is sometimes 

very difficult for a practicing clinician to know which vaccines to give because they do not know 

which vaccines patients have received. Some EMRs will report vaccines to the state registry, 

but people do not always live in one state. Currently, the registries do not speak back to the 

EMRs. She has patients who are over-vaccinated and others who are under-vaccinated due to 

this. Children and young adults cannot go to school or college unless they have immunizations. 

But there is not a similar check-up for adults who go to a new job unless they are in healthcare. 

A national immunization registry would help with this and improving the interface between 

registries and EMRs. 

Dr. Kempe said she very much supported the prospect of a national registry; however, they 

recently conducted a national survey of internists, family physicians, and pediatricians across 

the country. The unfortunate fact is that a very small minority of internal medicine physicians 

are using their state registries. A national registry is not going to work unless there is much 

more consistent use of registries by adult providers. She thought that was where they needed 

to go first. 

Vote: Adult Immunization Schedule 

Dr. Riley made a motion to approve the Adult Immunization Schedule. Dr. Romero seconded 

the motion. The motion carried with 14 affirmative votes, 0 negative votes, and 0 abstentions. 

The disposition of the vote was as follows: 

0 Opposed: N/A 

0 Abstained: N/A 

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ACIP recommended that there should be monitoring of the impact of the new recommendation 

in the target population of adults >65 years old, as well as continued monitoring of disease 

trends among PCV13-naïve adults 19 through 64 years of age without PCV13 indications, to 

evaluate the impact of herd effects and the long-term utility of routine PCV13 use among adults. 

In addition, ACIP is to be updated routinely on the changes in the vaccine-preventable disease 

burden among adults due to PCV13 direct and indirect effects during the next 3 years, and 

these data should inform revisions as needed to the proposed adult PCV13 recommendations in 

2018. 

Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Pneumococcal Vaccines 

Introduction 

Allison Kempe, MD 

Pneumococcal Vaccines Work (Arthur Reingold, Chair, unable to be present) 

Advisory Committee on Immunization Practices 

Dr. Kempe 

She reminded everyone that the Pneumococcal Vaccines WG’s terms of reference are to: 

 Review current data on efficacy, effectiveness, immunogenicity, and cost-effectiveness of 

pneumococcal vaccines; 

 Review current recommendations considering up-to-date evidence, including 

epidemiological studies conducted post-licensure, and assess strength of the evidence; and 

 Revise or update recommendations for pneumococcal vaccine use, as needed. 

As a reminder, ACIP recommended PCV13 for adults ≥65 years of age in August 2014. The 

WG conclusions at that time were that in the short-term, such a recommendation for universal 

PCV13 use in this age group was warranted for the opportunity to prevent disease for the 2014­

2015 respiratory seasons and for a number of additional years. However, the WG did realize 

that in the long-term, continued herd effects could limit the utility of such a universal 

recommendation. The magnitude of indirect effects were unknown, and there was uncertainty 

around the burden of vaccine preventable non-bacteremic pneumonia. 

Because of the recognition of this being a time-limited recommendation, the following statement 

was included in the ACIP vote: 

The recommendations for routine PCV13 use among adults >65 years old should be reevaluated in 2018 and revised as needed. 

During this session, updates were provided on the direct and indirect impact of PCV13 use on 

invasive disease among adults and children in the US; PCV13 impact among adults with chronic 

medical conditions with and without indications for PCV13 use; and the proposed research 

agenda to inform potential policy reconsideration in 2018 for PCV13 use among adults. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Direct and Indirect Impact of PCV13 on Invasive 

Disease Among Adults and Children in the US 

Tamara Pilishvili, MPH 

Respiratory Diseases Branch 

National Center for Immunization & Respiratory Diseases 

Centers for Disease Control and Prevention 

Ms. Pilishvili reminded everyone that in 2010, PCV13 replaced PCV7 in the US infant 

immunization schedule. In 2014, PCV13 was recommended for use in series with PPSV23 for 

all adults >65 years. The impact of PCV13 on invasive pneumococcal disease (IPD) among 

adults and children was evaluated. Data were used from the ABCs system to compare 

incidence as cases/100,000 population before PCV13 was introduced using the time period 

2007-2008 to post-PCV13 using the time period 2014-2015. 

With regard to trends in IPD incidence by serotype group in children under 5 years of age from 

2007–2015, dramatic reductions were observed in invasive infections shortly after 2010. These 

reductions continued through 2012. All of the reductions observed were driven by PCV13 

serotypes. From 2012 through 2015, the rates plateaued at around 2/100,000. 

Regarding the changes observed in individual serotypes, the most dramatic reductions in 

PCV13-type disease were driven by reductions primarily in serotypes 19A and 7F. These also 

were the only statistically significant reductions observed. Reductions were observed in 

serotype 3 disease, but they were not statistically significant. Also being monitored is whether 

any replacement disease is being observed due to non-vaccine serotypes. Thus far, no 

increases have been observed in non-vaccine serotypes. To put everything in perspective, Ms. 

Pilishvili showed the following graph of the overall impact of conjugate vaccines, PCV7 

introduced in 2000 and PCV13 introduced in 2010: 

In children under 5 years of age, overall invasive pneumococcal infections have been reduced 

from approximately 100/100,000 to about 9/100,000. Vaccine-type infections have been 

reduced to 2/100,000. This is a great success story. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

In terms of annual trends in IPD incidence among adults ≥65 years of age from 2007 through 

2015, when the pediatric vaccine was introduced, reductions also were observed in adult 

disease. The incidence among adults decreased from approximately 40/100,000 to about 25/ 

100,000 for overall infections. PCV13 types drove these changes with the introduction of the 

pediatric vaccine. Infections caused by PCV13 types in this age group are down to 

approximately 5/100,000. Looking at other serotypes that are included only in the 

polysaccharide vaccine, PPSV23 (11 serotypes not included in PCV13), or serotypes that are 

not included in any vaccine formulation, no significant changes have been observed at the 

population level. 

Regarding rate differences by serotype among adults ≥65 years from 2007 through 2008 versus 

2014 through 2015, PCV13 serotypes 19A and 7F essentially drove the reductions observed. 

These were statistically significant, but among adults, statistically significant decreases also 

were observed in serotype 3 infections. In 2014 and 2015, vaccine type IPD has plateaued and 

a slight increase in serotype 3 disease was observed. So far, the 2014 / 2015 increases 

observed in serotype 3 infection have not been statistically significant and it is unclear how to 

interpret this, but monitoring will continue. Very small magnitude increases have been observed 

in non-vaccine serotypes, with statistically significant increases only for type 23B IPD. With 

respect to trends in invasive pneumococcal disease among adults aged ≥65 years old from 

1998 through 2015, again, there were very dramatic reductions in invasive pneumococcal 

infections that were driven with the introductions of PCV7 and PCV13 serotypes. 

The following pie charts demonstrate how the serotype distribution has changed since 

introduction of PCV13 in adults: 

In 2007-2008, PCV7 serotypes accounted for 43% of invasive infections. In 2014-2015, that 

decreased to 22% of all invasive infections. In 2014-2015, serotypes that are unique to 

polysaccharide vaccine accounted for 36% of invasive disease and non-vaccine serotypes 

account for 42% of invasive disease. 

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<5 

5-18 PCV13 -84.78 (-91.04, -74.13)* 

ALL IPD -55.28 (-66.11, -41.00)* 

19-64 PCV13 -68.66 (-72.17, -64.72)* 

NVT -10.9 (-21.47, 1.08) 

>65 PCV13 -69.29 (-73.73, -64.10)* 

NVT -12.77 (-23.52, -0.50)* 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

This table shows the picture being observed across the age groups in terms of the impact of 

PCV13: 

* statistically significant decrease 

In summary, significant reductions were observed in PCV13-type IPD following the 5 years of 

PCV13 use. Reductions were driven by types 19A and 7F. There were significant decreases in 

overall IPD among children and adults. No significant changes were observed in non-PCV13 

types among children and adults. There were increases of a small magnitude of <0.5/100,000 

in select non-PCV13 serotypes. In 2010-2015, PCV13 use in children has prevented an 

estimated 280,000 IPD cases and 20,000 deaths among all ages. 

In conclusion, in the 5 years post-PCV13 introduction, significant reductions were observed in 

IPD caused by the PCV13 serotypes in children and adults, indicating continued direct and 

indirect effects. There has been no evidence of serotype replacement in children or general 

population of adults. 

Discussion Points 

Dr. Schmader (AGS) emphasized that 66 year olds are generally different from 88 years in their 

vulnerability to problems, and asked whether the data could be categorized in different age 

groups above 65 such as 70 through 79 and above 80. 

Ms. Pilishvili replied that they have stratified it across different age groups. The impact is 

similar. Obviously, 85 year olds have higher overall incidence of disease. In terms of 

decreases in PCV13 types and lack of strong replacement observed, it is similar across age 

groups. 

Dr. Bennett requested further information about why plateauing was occurring. 

139 

Age (years) Serotype group % change (95%CI) 

Non-PCV13 -5.77 (-34.63, 35.83) 

PPSV11 6.19 (-4.85, 18.52) 

PPSV11 -10.11 (-22.59, 4.39) 

ALL IPD -35.11 (-39.23, -30.72)* 

ALL IPD -36.47 (-41.42, -31.1)* 

PCV13 

Non-PCV13 

ALL IPD 

-86.82 (-90.59, -81.53)* 

-10.88 (-28.09, 10.44) 

-58.24 (-64.67, -50.65)* 

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Ms. Pilishvili responded that through 2014, reductions were observed in all PCV13 serotypes. 

From 2014 through 2015, there were plateaus or slight increases that were driven by serotype 

3. At this point, it is not statistically significant and the meaning of it is difficult to interpret. They 

will continue to monitor this. 

Dr. Romero asked how granular Ms. Pilishvili could get with regard to invasive disease. For 

example, could it be broken out by pneumococcal meningitis? In a consortium of 8 children’s 

hospitals, since the introduction of PCV13, there was not a decrease in the number of cases of 

pneumococcal pneumonia. There was a decrease in the number of vaccine strains, and there 

was a slight trend of increasing non-vaccine types. 

Ms. Pilishvili indicated that they can look at individual clinical syndromes. Some of those 

analyses are still ongoing. They did assess pneumococcal meningitis, and the trends they are 

seeing are similar. Although there seems to be more replacement observed with meningitis in 

the elderly. 

Dr. Gemmill (NACI) asked whether there was any information on coverage rates for children 

versus those over 65 years of age since the recommendation in 2014, to determine what type of 

impact that is having. 

Ms. Pilishvili indicated that the last presentation would address adult coverage. Pediatric 

coverage has been pretty stable. After the transition from PCV7 to PCV13, uptake was similar 

in the pediatric population. 

Dr. Whitley-Williams (NMA) asked whether there has been any reduction in the disparity gap 

between blacks and whites, particularly as it relates to IPD. 

Ms. Pilishvili responded that they have not analyzed this with the most recent data, but they 

have assessed the disparities and how those have changed post-PCV7 and shortly after PCV13 

was introduced. The disparities have been eliminated in terms of the PCV13 vaccine-type 

infections. However, the disparities still exist in terms of overall IPD caused by other serotypes. 

Dr. Whitley-Williams (NMA) asked whether that was due to the fact that other serotypes are not 

contained in the vaccine that are more prevalent in the black population. 

Ms. Pilishvili indicated that the distribution is similar overall. In later years, non-vaccine 

serotypes account for a higher proportion of infections. While the vaccine did prevent cases 

among various groups and reduced or eliminated those disparities, overall infections are caused 

by non-vaccine serotypes in every group. However, the disparities still exist in terms of the 

rates of disease cause by non-vaccine types. 

Dr. Sun (FDA) said his understanding was that the recommendation was subject to reevaluation 

because it depends on the challenges of sorting out the direct and indirect effects of the impact 

of PCV13 on the elderly. He asked how direct and indirect effects would be sorted out with 

these observed trends. 

Ms. Pilishvili requested that Dr. Sun hold this question until after her next presentation, during 

which she planned to discuss how direct and indirect effects would be sorted out. 

Dr. Stephens asked whether there are specific data on Alaska Natives and / or other susceptible 

populations among whom pneumococcal disease has been significant. 

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Ms. Pilishvili responded that ABCs does not have data on the Alaska Natives or other highly 

susceptible populations. Disparities are typically addressed in terms of racial disparities. There 

are studies ongoing in Alaska similar to the ABCs surveillance that monitors the trends and 

impacts of PCV13. She believes they see a similar impact of PCV13 introduction, with 

somewhat more replacement in the Alaska population than observed in the general US 

population. She deferred to Dr. Whitney for additional information. 

Dr. Whitney (SME) added that Alaska had very good impact quickly with PCV13 serotypes 

disappearing. They may have experienced a little bump up in the non-vaccine types. It is a 

population that needs to be observed more closely because they are susceptible to other 

serotypes, but it also is a population for which the numbers are small so it is hard to draw too 

much of a conclusion from the early figures. They will check this again and will provide 

additional information to ACIP. 

Ms. Groom (IHS) indicated that Johns Hopkins is continuing to monitor in the Southwest. In 

some American Indian populations, there is an ongoing disparity similar to what is observed in 

the African American population that continues to perplex them. They are contemplating ways 

to continue to tease that out. Great gains have been made with PCV13, but at the same time, 

they are still observing a disparity of IPD in the American Indian population. 

Changes in Invasive Disease Burden Among 

Adults With and Without Indications for PCV13 Use 

Sana Shireen Ahmed, MD 

National Center for Immunization & Respiratory Diseases 

Centers for Disease Control and Prevention 

The focus of Dr. Ahmed’s presentation was to discuss the impact of PCV13 on invasive disease 

among various groups of adults, with and without indications for PCV13 use. ACIP has 

recommended the 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent 

polysaccharide vaccine (PPSV23) for all adults 65 years and older and for adults 19 through 64 

years old with immunocompromising conditions. For immunocompetent adults <65 years of age 

with chronic conditions, such as heart disease or diabetes, only PPSV23 is recommended 

currently. Thus, this subgroup of adults with no PCV13 indications is experiencing only indirect 

PCV13 effects through PCV13 use in children. 

The objectives of this study were to: 1) evaluate PCV13 impact in terms of direct and indirect 

effects on IPD burden among adults 19 through 64 years of age, with and without current 

indications for PCV13 use; 2) estimate remaining vaccine preventable IPD burden among adults 

19 through 64 years old with select medical conditions in 2013–2014, following 4 years of 

PCV13 use in children. 

For the numerators, IPD cases were identified through the ABCs system, a laboratory and 

population-based surveillance system ongoing at 10 sites. An IPD case was defined as 

isolation of pneumococcus from a normally sterile site. For the denominators, the National 

Health Interview Survey (NHIS) was used to estimate the US population of adults. NHIS is a 

data collection program of the CDC’s National Center of Health Statistics (NCHS). It is a crosssectional survey with interviews administered to households and non-institutional groups 

throughout the year. The analysis included ABCs IPD cases among adults 19 through 64 years 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

of age with and without select chronic conditions, and corresponding NHIS population 

denominators. 

Adults with the following conditions were identified within ABCs and NHIS and were placed into 

three groups: 

Conditions and risk factors for which there are current indications for PPSV23 vaccination alone 

will be referred to as “PPSV23-only indications group” shown on the left. Adults with 

immunocompromising conditions for which PCV13 and PPSV23 are recommended will be 

referred to as “adults with PCV13 indications.” Please note that HIV and renal failure, both 

current indications for PCV13 use, were not included in this analysis due to NHIS data 

limitations. Healthy adults in the same age group who did not have any of the medical 

conditions listed above will be referred to as the “healthy group.” 

In order to compare the effects of PCV13 use on IPD burden among adults 19 through 64 years 

of age with select conditions, two distinct periods were assessed during the 2007-2014 period. 

PCV13 replaced PCV7 in 2010 for use among children, so anything prior to 2010 was 

considered pre-PCV13, the baseline. From 2010-2014, adults were experiencing PCV13 

indirect effects. This is considered to be the post-PCV13 era. In 2012, PCV13 was 

recommended for use among adults with immunocompromising conditions. Since 2012, healthy 

19 through 64 year old adults and adults with conditions for which only PPSV23 is 

recommended continued to experience indirect PCV13 effects. Since 2012, adults with PCV13 

indications have been experiencing both direct and indirect vaccine effects. Therefore, in order 

to evaluate PCV13 effects on burden, a pre-PCV13 baseline for the period 2007-2008 was 

compared to the post-PCV13 period 2013–2014. 

To address the first objective, estimates were calculated for IPD incidence, percent changes in 

overall and PCV13-type IPD incidence between the 2 periods, and the contribution from direct 

and indirect effects on overall impact among adults with PCV13 indications. Overall, IPD rates 

declined among healthy adults from 8/100,000 to 4/100,000 with a 47% decline in overall IPD 

rates. Among adults with PPSV23-only indications, IPD incidence declined from 15/100,000 to 

12/100,000 with a 19% decline. Among the group with PCV13 indications, IPD rates declined 

from 36/100,000 to 27/100,000 persons with a 24% decline. To further understand the primary 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

drivers of these declines in IPD rates, the burden was broken down by serotype groups. This 

table shows IPD incidence pre- and post-PCV13 and percent changes in the last 3 columns by 

serotype group and presence of vaccine indication: 

The serotypes were grouped as PCV13-types, the 11 serotypes unique to PPSV23 labeled as 

“PPSV23 unique,” and non-vaccine types, which includes serotypes not covered by any 

vaccine. Looking at the rate changes across serotype groups, the reductions in overall IPD 

rates are driven by declines in PCV13 IPD rates. PCV13 IPD rates declined by 73% in the 

healthy group and by 57% among adults with and without indications for PCV13 use. Similar 

absolute changes in rates among healthy adults and adults with PPSV23 indications 

demonstrate that both groups experience similar indirect effects from child vaccination. Similar 

percent declines in IPD incidence were seen in adults with and without PCV13 indications, 

suggesting that the adults with vaccine indications largely experienced indirect effects. In 2013­

2014, PCV13-type IPD rates were low across all groups. No reductions or increases were seen 

in IPD caused by PPSV23 unique serotypes across all condition groups, and no evidence of 

replacement disease was seen in non-vaccine type IPD across condition groups. 

This bar graph demonstrates the disease incidence and underlying conditions among adults 19 

through 64 years old by serotype groups 3 to 4 years after PCV13 introduction: 

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To estimate the contribution from direct effects alone, additional assumptions were made. 

Vaccine coverage was assumed to be about 5% to 7% based on a recent study estimating 

cumulative PCV13 uptake through 2014 for adults 19 through 64 years with current PCV13 

indications. Also assumed was that vaccine efficacy was 74% against vaccine type IPD based 

on the results of an efficacy trial in HIV+ adults and similar to IPD efficacy in adults >65 years 

old from the CAP Immunization Trial in Adults (CAPiTA). The number of cases prevented from 

direct PCV13 effects is the factors of baseline PCV13 type IPD burden, vaccine coverage and 

vaccine efficacy. Given these assumptions, it was estimated that approximately 33 to 46 cases 

would be expected to be prevented from direct protection afforded by PCV13 use in adults. The 

remaining 584 to 597 cases would have been prevented through indirect PCV13 effects. These 

estimates demonstrate that in a setting of 5% to 7% coverage with PCV13, 93% to 95% of the 

observed impacts in 2013-2014 is expected to be due to indirect or herd effects from childhood 

vaccination. If higher PCV13 coverage of 20% is assumed, similar to the current PPSV23 

coverage in adults <65 years old with vaccine indications, the number of cases estimated to be 

prevented directly by PCV13 increases, decreasing the proportion prevented through indirect 

effects to 79% of observed total PCV13 impact. In a setting of remaining vaccine-preventable 

disease burden, the relative contribution of direct PCV13 impact increases with increase in 

vaccine coverage among adults. 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Looking across the different conditions, overall incidence rates were higher among adults with 

select medical conditions compared to the incidence of 4/100,000 in healthy adults. The rates 

among those adults with chronic medical conditions ranged from 10/100,000 for adults with 

heart disease to 136 / 100,000 for adults with hematologic malignancy. In addition, the largest 

burden of disease for all groups was caused by serotypes not covered by PCV13 as shown in 

the yellow bars. The incidence of PCV13 type IPD ranged from 2/100,000 to 12/100,000 in 

adults with PPSV23-only indications to 4/100,000 to 21/100,000 adults with PCV13 indications 

and accounted for 16% to 28% of all IPD. PPSV23 unique serotypes and non-vaccine type IPD 

accounted for 71% to 84% of overall IPD burden. 

In order to estimate the contribution from direct and indirect effects on observed reductions in 

IPD among adults with PCV13 indications, adults with hematologic malignancy were chosen as 

a demonstration example since it is a group for which PCV13 has been recommended since 

2012. In this group, a contribution is expected through both the direct and indirect effects of 

PCV13. An estimated 890 cases of PCV13-type IPD would be expected to be observed among 

adults with hematologic malignancy in the US with pre-vaccine IPD rates applied to the 2013­

2014 population of adults with hematologic malignancy. There were an estimated 260 cases of 

PCV13-type IPD observed in adults with hematologic malignancy in 2013-2014. For simplicity, 

it was assumed that the observed burden in the post-PCV13 era was influenced only by PCV13. 

It was also assumed that there were no PPSV23 effects, and that PCV13 direct and indirect 

effects had an additive impact on disease burden. With those assumptions, it was inferred that 

the difference in the number of estimated cases between the time periods is the number of 

cases prevented by direct plus indirect effects. There were 630 cases prevented by PCV13 

effects. 

There were several limitations to the study. NHIS population estimates and ABCs IPD 

estimates were obtained using different methodologies. Groups from ABCs and NHIS are 

subject to misclassification bias. Because of the limitations in the data sources, vaccine impact 

among adults with HIV and dialysis could not be evaluated and, due to the same data 

limitations, these groups could not be excluded from the healthy group, so the incidence 

estimate for this group may be an overestimate. Medical conditions were not mutually exclusive 

and interactions may exist. However, similar trends in disease burden were seen when certain 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

groups were restricted to adults with only one condition. The analysis was focused on IPD and 

did not include community-acquired pneumonia (CAP), which contributes to the largest burden 

in adults. The burden of vaccine-preventable pneumonia should be considered for estimating 

overall impact on pneumococcal disease burden. 

In summary, the investigators found that that PCV13 introduction among children reduced 

incidence among healthy 19 through 64 years old adults and those with underlying conditions. 

Reductions of a similar magnitude were observed in those with and without PCV13 indications 

in the context of low PCV13 coverage, suggesting that observed benefits to date are largely due 

to indirect PCV13 effects. Adults with underlying conditions still continue to experience higher 

IPD rates compared to healthy adults in the post-PCV13 period, but most of the remaining 

burden of IPD in adults is from non-PCV13 serotypes with little remaining PCV13 disease. 

There is no evidence of serotype replacement disease among these groups of adults. 

Discussion Points 

Regarding the risk groups, Dr. Maldonado (AAP) pointed out that for diabetes or smoking, the 

risk is lower but the population base may be higher. She asked whether Dr. Ahmed thought the 

indirect impacts may be larger and if she looked at any others besides the immunologic 

malignancy group for the rough estimation. 

Dr. Ahmed responded that for the rough estimation, they looked at that group because PCV13 

already was indicated for them. They were able to distinguish between direct and indirect 

effects. 

Dr. Bennett pointed out that so far, PCV13 is not recommended for risk groups other than those 

who are immunocompromised, in that age group. 

Dr. Maldonado (AAP) suggested that they still could look at a larger burden of disease for 

indirect effects. 

Dr. Atmar asked whether instead of subtracting the direct effects from the total cases, they 

considered coming at it from the other direction and looked at the impact of the indirect effects, 

assuming they were similar for what was observed in groups for whom PCV13 is not indicated. 

It looked like the magnitude of decrease was similar, so they might be able to better estimate 

about the direct effects by taking that approach to get the range. 

Dr. Ahmed responded that they did not take that approach in the calculations, but agreed that it 

was another way they could consider looking at it. 

It seemed to Dr. Zahn (NACCHO) that in the past when they assessed indirect effects when 

PCV7 was introduced, the indirect effects for high risk populations was not as impressive. That 

is, indirect protection of non-high risk individuals was better than high risk individuals. This 

seemed somewhat different from that in a better way. He wondered whether it actually was 

different or if the data they have now is just more robust in terms of teasing out the answer to 

that question. 

Dr. Ahmed said she thought historically looking at PCV7, there were similar effects even for high 

risk groups at that time. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Moore observed that this study did not include any assessment of CAP. She asked whether 

studies were underway or were being planned to assess any impact on CAP. 

Dr. Ahmed indicated that Ms. Pilishvili would address this in the next presentation. 

Dr. Lee noted that Dr. Ahmed’s presentation was very elegant, pointing that it was a lot of 

complicated data and Dr. Ahmed did a really nice job presenting it visually. Similar to Dr. 

Atmar’s question, she wondered whether Dr. Ahmed could do a sensitivity analysis by flipping it 

to take an indirect effects perspective since she came up with estimates for the herd protected 

only groups. She said part of her rationale for thinking about this was because it was easy for 

her to believe that for the general population, the vaccination rates are 5% to 7%, but it was 

harder for her to believe that the vaccinations rates are that low for the immunocompromised 

population. She wondered whether Dr. Ahmed could back into it that way to come up with 

guesstimates of vaccine delivery in that population to see if that actually quantitatively makes 

sense. It would at least offer two different bounds. 

Dr. Ahmed indicated that in terms of vaccine coverage, what she listed as 5% to 7% was for 

those 19 through 64 years of age with current PCV13 indications. She agreed that the 

coverage rates for each condition group might vary, with some higher and lower, so depending 

on coverage they may be afforded a higher level of protection if they are higher coverage. 

Dr. Lee suggested that it might also be helpful to capture mean and median age of the 

population of those with chronic conditions, in part from the pediatric perspective because she 

feels like they see a lot of families. If the median age is among families and young children, it 

might make sense that their exposure is just inherently different than another population that is 

either much older or much younger. 

Dr. Bennett asked whether a sensitivity analysis was performed looking at the immunization 

rates. That does seem to drive the analysis to a large extent. It was surprising to her even that 

among people with a hematologic malignancy, the vaccination rates would be only 20%. It 

seems that they would be higher. 

Dr. Hunter said he was not surprised from an implementation point of view based on his 

experience in the City of Milwaukee. The health department was asked to come to a tertiary 

care center to provide vaccination services, because they were not able to provide it within the 

subspecialty clinics. Based on some manuscripts he has seen related to a hematologic 

malignancy, the vaccination rates for that particular condition were quite low. He was really 

surprised about that. He wondered why they thought specialists would do any better job than 

primary care physicians. 

Dr. Cohn requested clarification about whether the coverage estimates Dr. Ahmed used were 

for any pneumococcal vaccine or just for PCV13, and how the question was asked in the survey 

from which the 5% to 7% was obtained. 

Dr. Ahmed replied that that analysis was done by Pfizer which assessed uptake and did 

modeling, which showed that among those 19 through 64 years of age in high risk groups that 

included immunocompromised individuals, PCV13 coverage was about 5% to 7%. 

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Dr. McLaughlin (Pfizer) said the first thing to note about uptake is that it is a very difficult 

question. The way they addressed it was through a multifactorial approach. The easiest way to 

do it is to look at IMS Health claims uptake, which are claims for the vaccine. The difficulty is by 

just looking at the claims, some claims are missed that might have occurred in the pharmacy or 

a specialty office that are not typically captured by an entity like IMS Health. They also looked 

at Pfizer’s internal sales data. Even though sales data are not split by pediatric and adult, they 

tried to parse it out by which practices the claims came from. Essentially, they looked at the 

IMS claims data and then factored that to what they were seeing in the sales data to try to get 

an overall picture of not just claims from health insurance, but also missed claims that were 

showing up in their sales. For risk groups, the numbers are probably a slight underestimate 

because not only is it more difficult to get data from these specialty clinics, but also it is more 

difficult to know what the underlying health status is of people with these claims. That has to be 

based on claims rather than a medical record. It is more likely that coverage will be 

underestimated in the risk groups than in the general population. 

Outline of Research Agenda to Inform Potential 

Policy Change in 2018 for PCV13 Use Among Adults 

Tamara Pilishvili, MPH 

Respiratory Diseases Branch 

National Center for Immunization & Respiratory Diseases 

Ms. Pilishvili indicated that lastly during this session, the WG wanted to share with the 

committee a roadmap of how the WG plans to approach the potential policy consideration in 

2018 for PCV13 use among adults. She highlighted some of the key ongoing studies that will 

help contribute to this evidence that the WG will share with the committee in 2018. The WG 

thought that in order to address the potential policy reconsideration in 2018, the following basic 

but key questions need to be answered before the 2018 review: 

 Is PCV13 use preventing disease among adults >65 years old? 

 To what extent are the observed benefits driven by adults PCV13 use (direct effects) versus 

pediatric PCV13 use (indirect effects)? 

 What benefits would be expected from continued PCV13 use among adults versus 

reconsidering this policy? 

For each of these questions, Ms. Pilishvili presented on the types of studies the WG believes 

will be helpful in answering the questions and highlighted some of the methodologies and 

objectives for some of the key ongoing studies. 

In terms of the first question regarding whether PCV13 use is preventing disease among adults 

>65 years old, the obvious study and action is to continue monitoring the impact of new 

recommendations in the vaccine target age group. In order to understand how much of the 

impact being observed can be attributed to the direct PCV13 effects in adults, it is important to 

understand changes in the IPD burden before and after PCV13 recommendation; changes in 

pneumococcal pneumonia burden before and after PCV13 introduction; uptake of vaccine 

among adults >65 years old; and the effectiveness of PCV13 and PPSV23 against IPD among 

adults >65 years old. CDC is conducting a PCV13 case-control effectiveness study among 

adults >65 years of age. The idea is to determine how the new recommendations work in the 

US population. 

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With respect to the second question regarding the extent to which the observed benefits are 

driven by adults PCV13 use versus pediatric PCV13 use, the data shared thus far demonstrate 

the indirect effects that have been observed to date. That is important for IPD, but it also is 

important to assess the same data for pneumonia. It is important to continue to monitor the 

impact of PCV13 use in children on adult disease burden to assess changes in IPD and 

pneumonia among adults >65 years old before and after PCV13 introduction for children and 

before PCV13 recommendations for adults; and changes in IPD and pneumonia among adults 

<65 years old without current PCV13 indications. This will allow for assessment of the indirect 

effects observed to date to determine whether the indirect effects will continue or have 

plateaued. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Colonization studies are important among adults and children to understand the residual 

circulation and transmission of PCV13 types in a setting of herd effects in the community. 

Disease trends will continue to be monitored through 2018 to estimate the contribution of direct 

versus indirect effects to observed reductions in IPD and pneumonia. What is being observed 

are direct and indirect effects combined, so it will be challenging to tease those effects apart. 

Therefore, several approaches are being taken that involve mathematical modeling to 

understand the contribution of direct versus indirect effects. This will rely on understanding of 

vaccine uptake and how much of the observed reduction can be attributed to direct effects. 

There also is the PCV7 experience on indirect effects, as well as indirect effects post-PCV13 

that are still being observed in certain adult age groups that will allow for projection of what the 

expected continued indirect effects should be. These studies will be important for IPD as well 

as pneumonia. 

In terms of the impact on PCV13-type IPD burden among adults >65 years of age, PCV13-type 

IPD rates declined through 2014 due to indirect PCV13 effects. No additional declines were 

observed in 2015 and appear to have plateaued. PCV13-types accounted for 22% of IPD in 

2015 compared to 43% pre-PCV13. Continued monitoring of disease trends among adults <65 

years old is needed to evaluate the impact of herd effects. PCV13-type IPD burden continues 

to decline among adults without current indications for PCV13 use. PCV13-types accounted for 

24% of IPD in 2014 compared to 48% pre-PCV13 among adults without indications for PCV13. 

PCV13 case-control effectiveness study among adults ≥65 years of age mentioned earlier is 

ongoing, with the objectives were to: 1) evaluate the effectiveness of PCV13 against PCV13­

serotype invasive pneumococcal disease; and the effectiveness of PCV13 and PPSV23 when 

given in series; and 2) evaluate risk factors for IPD among adults >65 years of age in a setting 

of PCV13 and PPSV23 use when given in series because this is the recommendation for adults 

>65 years of age. Cases of IPD among adults >65 years old are identified through ABCs. 

Pneumococcal isolates are serotyped, so they will be looking at the very specific endpoint of 

vaccine-type disease. Controls are being identified using a commercial database, with a goal to 

enroll 4 controls per case matched on age group and zip code of residence. For both cases and 

controls, vaccination histories are being obtained by identifying all medical care encounters and 

providers in the last 6 years, and then attempting to contact each of these providers who may 

have provided vaccines to the participant. 

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To date, 200 cases and 520 controls have been enrolled. Pneumococcal serotyping is ongoing 

to determine the number of vaccine-type (VT) cases that have been enrolled so far. In terms of 

the projection of the sample size estimates, at approximately 30% PCV13 coverage, the sample 

size estimation suggests that approximately 46 VT cases will be needed to demonstrate a VE of 

75%. Enrollment began in about November 2015 and it is estimated that the end of enrollment 

will be in winter 2017-2018, based on the VT cases occurring and increases in coverage. 

CAP is also a very important endpoint. The policy decision in 2014 was largely driven by the 

estimated vaccine-preventable burden of community-acquired pneumonia. Therefore, studies 

to monitor PCV13 impact on pneumococcal pneumonia are ongoing and are very important in 

contributing to review in 2018. Ms. Pilishvili highlighted three ongoing studies assessing various 

endpoints: 

 A CDC study assessing the impact of PCV13 on all-cause pneumonia hospitalizations 

 CDC population-based surveillance for non-invasive pneumococcal pneumonia 

 Population-based surveillance for PCV13-type pneumococcal pneumonia being conducted 

at the University of Louisville, funded by Pfizer 

The objectives of the CDC study assessing the impact of PCV13 on all-cause pneumonia 

hospitalizations are to: 1) measure the impact of PCV13 introduction in children on pneumonia 

hospitalizations across all age groups in terms of PCV13 indirect effects only; and 2) estimate 

the additional impact of the 2014 adult PCV13 recommendation on pneumonia hospitalizations 

among adults ≥ 65 years of age in terms of PCV13 direct effects. This is to tease apart the 

direct and indirect effects. For the first objective, the data source is statewide inpatient data 

from 2004-2014. The study methodology is a time-series analysis using “synthetic controls” to 

adjust for unmeasured confounding (e.g., changes in coding practices, change in healthcare 

seeking behavior). For the second objective pertaining to adults ≥ 65 years of age, the data 

source is statewide inpatient data from 2004-2014 and the CDC is collaborating with CMS to 

use Medicare Part B beneficiary data from 2008-2016 to assess hospitalizations and 

vaccination status. The study methodology is a time-series analysis using “synthetic controls” to 

adjust for unmeasured confounding with two intervention points, 2010 and 2014. Because 

these are administrative data using ICD-9 codes, a control measure is needed, so the new 

method of using synthetic controls has been proposed in order to adjust for unmeasured 

confounding. In terms of the outcomes, CDC is using the classification algorithm based on 

discharge codes to assess all-cause CAP and pneumococcal pneumonia hospitalizations. 

The objectives of CDC’s population-based surveillance for non-invasive pneumococcal 

pneumonia are to: 1) conduct population-based surveillance for noninvasive pneumococcal 

pneumonia for 2013 and onward; 2) measure the burden of non-invasive pneumococcal 

pneumonia in adults; and 3) measure the potential impact of adult PCV13 recommendations. 

This expands and builds on CDC’s ABCs that conducts surveillance for invasive disease. 

Through the same sites, they are expanding to include non-invasive pneumonia in the 

surveillance. The case definition for this surveillance is positive pneumococcal urine antigen 

test (UAT) from January 2013 onward, hospitalized adult ≥18 years of age who are residents of 

the surveillance area, clinically or radiographically-confirmed pneumonia documented in the 

medical record, and no evidence of invasive disease. The catchment area includes 15.6 million 

persons. Hospitals are included that offer the UAT. In order to obtain incidence estimates, 

adjustments will be made to account for the fact that not all at-risk patients are tested by UAT at 

hospitals offering it, and not all hospitals in the catchment area offer UAT. 

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The objective of the population-based surveillance for PCV13-type pneumococcal pneumonia 

being conducted at the University of Louisville is to estimate the incidence and outcomes of 

hospitalized CAP among adults >18 years old in 9 adult hospitals. This is an active prospective 

population-based cohort. They are able to estimate the denominators of the catchment area 

and, therefore, estimate the incidence of CAP among adults. They have a very stringent 

inclusion criterion, which is pulmonary infiltrate on chest x-ray + >1 of the following: 

cough/sputum, or fever/hypothermia, or leukocytosis/leukopenia and no alternative diagnosis. 

Perhaps the only study that will look at more specific outcome of VT pneumococcal pneumonia, 

the serotype-specific urine antigen detection (SSUAD) study, is also funded by Pfizer and is 

ongoing at 20 hospitals. The objective of the SSUAD study is to estimate the proportion of adult 

CAP caused by PCV13 serotypes among adults >18 years of age. This is active prospective 

hospital surveillance that includes subjects who presented with suspected pneumonia and 

positive chest x-ray for CAP and had a discharge diagnosis of CAP. 

 

 

 

 

 

Measuring vaccine uptake of PCV13 and PPSV23 in the target population of adults >65 years 

old is crucial in order to understand the contribution of the direct effects and attribute the 

observed impact of vaccine use among adults. PPSV23 coverage has been assessed through 

the NHIS annually. PPSV23 coverage has been relatively stable through 2014 at 59.7% to 

62.3%. A limitation of the survey is that the current survey question does not distinguish 

between PCV13 and PPSV23. In terms of PCV13 and PPSV23 coverage assessment since the 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Each of these studies has its own set of challenges in terms of monitoring the impact on 

pneumonia. The endpoint for the first study is all-cause CAP, which is a non-specific endpoint 

that may limit the ability to detect reductions of small magnitude. In addition, any replacement 

with non-vaccine types may wash out the effects that might be detected looking at all-cause 

CAP as an endpoint. To further complicate and add to the challenge, changes from ICD-9 to 

ICD-10 overlap with the vaccine introduction period for adult immunization with PCV13. 

Therefore, it will be important to eliminate bias that is related to the coding using ICD-10 codes. 

To address this, cross-validation studies are being conducted mapping ICD-9 algorithms to ICD10 code algorithms. 

For the study using the UAT to assess pneumococcal CAP, UAT does not distinguish 

pneumococcal serotypes. Again, replacement with non-vaccine types may wash out the effects. 

UAT sensitivity is 50% to 80% among non-bacteremic patients, so it may underestimate the 

burden. PPSV23 receipt prior to UAT or carriage may influence test results. For the PCV13­

type CAP study, SSUAD is not commercially available so the results will be limited to this one 

study. SSUAD does not detect non-PCV13 serotypes, and PPSV23 receipt prior to UAT or 

carriage may influence test results. 

As mentioned earlier, adult pneumococcal colonization studies are important to understand 

what strains are circulating in the community and what the residual circulation and transmission 

are of the VT strains in a setting with pediatric use of the vaccine, as well as the adult use of 

PCV13. To that end, CDC is conducting an adult pneumococcal colonization study. The 

objectives of this study are to: 1) define the prevalence and serotype distribution of S. 

pneumoniae carriage in seniors; 2) assess risk factors for colonization; and 3) provide baseline 

data to assess the impact of the new ACIP recommendation on carriage rates through later 

carriage studies. The study population is adults 65 years of age or older enrolled at outpatient 

clinics and senior centers who are not severely immunocompromised. Both nasopharyngeal 

(NP) and oropharyngeal (OP) swabs are being obtained, and vaccination history is being 

collected. To date, 2773 participants have been enrolled across 4 US states. The target is to 

enroll 3353 participants. Enrollment will continue through December 2016. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

2014 recommendations, CMS data have been used for PCV13 and PPSV23 claims to estimate 

coverage among Medicare Part B beneficiaries. It is important to note that the Medicare 

Advantage Plus population is excluded from the CMS data analysis because CDC does not 

have access to those data. Based on the results of the CMS claims data analysis through 

October 2015, PCV13 uptake was 15.86% and PPSV23 uptake was approximately 45%. 

PPSV23 coverage is likely an underestimate based on other sources of information CDC has on 

PPSV23 coverage, so not including the Medicare Advantage Plus population might lead to 

some underestimate of the PCV13 coverage related to the data being limited to Part B 

population only. 

In the study that was referred to in Dr. Ahmed’s presentation, analysis of vaccine sales and 

Insurance Management Services (IMS) claims were used to estimate PCV13 coverage1,2. 

Modeling was done to attribute the vaccine doses given to adults versus children in various 

populations. Through July 2016, uptake of PCV13 by adults ≥65 was approximately 40%. At 

the end of 2015, uptake was estimated to be approximately 31% using the IPD data. In highrisk individuals 19 through 49 years of age, coverage was estimated to be 11%. Among highrisk individuals 50 through 64 years of age, coverage was estimated to be 10% [1QuintilesIMS, 

Anonymized Patient-Level Data (APLD), Oct 2016 (includes diagnostic and prescription 

utilization claims for PCV13); 2 Pfizer, Inc. internal sales data for PCV13, Oct 2016]. 

In terms of the third question regarding what benefits would be expected from continued PCV13 

use among adults and how direct and indirect effects could be teased apart, CDC is developing 

a mathematical model to evaluate the impact potential changes in the adult recommendations 

would have on the adult disease burden, given observed and expected herd effects ofthe 

pediatric PCV13 program. Again, the key from all of the parameters and data inputs presented 

is to estimate the relative contribution of the direct versus indirect effects on the adult disease 

burden. CDC will evaluate various policy options, including removal of the PCV13 

recommendation versus continued use. The outcomes for each policy option will include the 

potential public health impact of changing the policy, including the cost-effectiveness. 

The next steps are to continue to update ACIP on the changes in vaccine-preventable disease 

burden among adults due to PCV13 direct and indirect effects during the next 2 years, and 

update ACIP on the results of the ongoing studies. These data should inform revisions as 

needed to the proposed adult PCV13 recommendations in 2018. The declining burden of 

PCV13-type disease among adults over 65 years of age due to indirect effect of vaccinating 

children may signal that PCV13 is no longer needed. A revised cost-effectiveness evaluation 

incorporating changes in disease burden, uptake, and the cost of the vaccines will help align 

this recommendation with other adult vaccines in use. 

In conclusion, Ms. Pilishvili posed the following questions for ACIP’s consideration and 

discussion regarding a potential policy change in 2018: 

 Is the proposed research agenda appropriate to help determine if a policy change is needed 

in 2018? 

 What additional information will the committee need to help determine in 2018 whether 

continued PCV13 use in adults is warranted? 

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Discussion Points 

Regarding the National Health Interview Survey on slide 14, Ms. Pellegrini asked whether that 

survey requests permission to correlate answers against patients’ medical records. 

Ms. Pilishvili replied that there is no cross-check with any medical or vaccination records for this 

survey. 

Ms. Pellegrini said she was not sure she would be confident of the quality of responses from 

that survey. It is one thing to ask people if they have received one pneumococcal vaccine, but 

to expect them to know that they received both and if so, which one first and which one second 

may not be terribly useful. 

Ms. Pilishvili said this was exactly the discussion that had been ongoing in terms of trying to 

determine whether they can use this survey to understand which vaccines have been given. 

For self-report, it is not expected that people would remember. 

Dr. Belongia said he had one note of caution on the studies related to all-cause CAP based on 

his own research. In the influenza vaccine world, they learned about a decade ago that they 

could get wildly inaccurate estimates if they based their endpoint on a non-specific 

administrative data source. Fortunately, NCIRD has other studies planned that will assess very 

specific pneumococcal and serotype specific outcomes, so he thought that was good. He asked 

what a “synthetic control” is. 

Ms. Pilishvili replied that this new methodology has been proposed by Dr. Dan Weinberger at 

Yale for the analysis of administrative data on CAP hospitalizations, which has been presented 

as an improved methodology to use administrative data to evaluate impact of vaccines. The 

idea behind his methodology is that in previous studies where administrative data were used to 

document the impact of PCV7 or PCV13, as a control measure/condition, specific ICD-9 codes 

unrelated to pneumonia diagnosis have been used such as fractures. Whereas, the 

methodology of synthetic control, rather than using a single ICD-9 code or single condition as a 

control, creates a composite control that adjusts for potential changes that may be occurring 

with each individual condition. It optimizes the control of potential bias due to changes to coding 

practices, or some inherent trends in any particular condition. 

Dr. Stephens was struck by the fact that there was not a lot of emphasis on molecular typing or 

whole genome analyses. He knew they were doing whole genome analyses on most of the 

invasive isolates now. A lot was learned about 19A emergence in the replacement era with 

PCV7 through that methodology, and he wanted to get Ms. Pilishvili’s comments about the role 

of molecular typing as it relates to these studies. 

Ms. Pilishvili responded that in the ABCs surveillance, they are moving toward whole genome 

sequencing (WGS). This is still new and she does not think they have solidified how it will 

contribute to this particular question. Certainly, in terms of monitoring the trends and the 

emergence of new strains, they plan to use the WGS data. 

Dr. Moore asked whether they are using immunization information systems (IISs) as a source 

for data for adult immunizations. It is hard for people to remember what they have had. Almost 

all states have lifelong registries, some of which are outstanding and would have good 

information on exactly what kind of vaccines people have had. It would be a great resource 

rather than recollection and other less direct methods. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Dr. Bennett pointed out that this is somewhat problematic because the adult registries are fairly 

new in most states, so the data for adults is not as good as it is for children. 

Dr. Mel Kohn (Merck) raised the issue of series completion. The recommendation from ACIP 

includes both vaccines. He expressed his hope that series completion would be taken into 

account when the WG reevaluates the recommendations. Merck has reviewed some of the IMS 

data to determine how many of the people who received PCV13 went on to receive a second 

vaccine of PPSV23. The early indication with about 20 months of follow-up for the first month’s 

cohort after the recommendation was passed suggests very low rates of about 12%. As they 

move into influenza season, he expects that number will increase. He said this also was an 

exhortation to anyone listening to go ahead and complete that series. He believes that yet 

another factor that will be important for the WG to consider is how well the series is being fully 

implemented. 

Dr. Bennett agreed that many complexities to implementation are being observed in different 

settings that are not ideal, and they will want to try to figure that out. 

Dr. Gemmill (NACI) indicated that Canada has not made a recommendation for use of PCV13 

for healthy people over 65 years of age. They are very interested in all of these results, and 

may even look upon it as an opportunity to collaborate. 

Dr. Paradiso (Paradiso Biologics Consulting) noted that it appeared that the indirect effect in the 

19 through 64 year old healthy population was in the 70% range; whereas, in the high risk 

populations, the indirect effect was about 57% for the indications for polysaccharide or 

conjugate. There was an earlier discussion about a distinction or differences in those 

populations. He thought those would be interesting to look at, because when trying to estimate 

based on the coverage, what portion was direct and indirect, those differences will be important. 

In the case-control studies, they distinguished populations of people who got the conjugate 

based on whether they got it before or after polysaccharide. Many of the over 65 year olds 

would have had previous polysaccharide. It would be interesting to see the difference between 

those who had polysaccharide previously, and then subsequently got a conjugate vaccine. 

Ms. Pilishvili replied that in their case-control study, they are identifying indication period or lookback period for both cases and controls. They are contacting providers and obtaining history of 

PCV13, PPSV23, and any other vaccines they have received. If they have sufficient power to 

look at various schedules, they certainly will be interested in looking at the sequence in which 

the vaccines were received as well. She agreed that the impact in terms of the ratio measure 

they have seen in healthy adults versus those with underlying conditions is higher; however, 

looking at the percent reductions alone is not quite sufficient. That is why they look at the 

absolute change as well. Looking at the absolute changes in rates, they actually were quite 

similar among healthy and those with underlying conditions. Taking both pieces of evidence 

into account, as well as looking at the remaining vaccine-preventable disease burden in both 

healthy and those with indications, and understanding what it means at the population level is 

important. 

Dr. Hunter expressed concern about the cost of missed opportunities to vaccinate, and errors in 

vaccination that can occur when there are complicated recommendations for high risk 

individuals who have a higher rate of vaccine-preventable diseases. There are large numbers 

of lower risk healthy people who have lower risks of vaccine-preventable diseases. But if there 

are very complicated recommendations to implement the vaccine administration, people who 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

actually administrate the vaccines will be confused. He wondered if there was any way to 

capture in the research whether increasing the complexity of the vaccine recommendation for a 

small group of people affects the uptake amongst a large group of people. 

Ms. Pilishvili thought this was a very good point that they would have to think about. 

Dr. Sun (FDA) said he was struggling to understand how to tease out the indirect effect from an 

increase in the coverage rate of PCV vaccination for the elderly. One might imagine that there 

would be some indirect effect from having other elderly people around you vaccinated and, 

therefore, less pneumococcal disease, and the additional indirect effect on not being exposed to 

young children who do not carry pneumococcus as a result of vaccination. That is, the indirect 

effect from adults versus the indirect effects from children. 

Ms. Pilishvili responded that this would not be simple, which was why they were proposing 

several approaches. It will not be simply subtracting one from the other, although there was a 

nice demonstration in Dr. Ahmed’s presentation. Going forward, especially in the population 

that is receiving the vaccine and also experiencing the indirect effects, they will have to learn 

from the past data what the observed indirect effects have been and what is expected projecting 

those indirect effects, of course, making certain assumptions, and also understanding what the 

contribution of direct effects is by measuring the coverage and estimating what the contribution 

of the direct effects to indirect effects would be going forward. Though the answer is not simple, 

they have certain models that they are developing that will take into account various scenarios 

based on the observed data they have, and the data they will continue to observe in terms of 

indirect effects among adults who are not currently receiving the vaccine. This will be done 

using the modeling approach and performing various sensitivity analyses, because certain 

assumptions will have to be made as far as projecting the indirect effects going forward. 

Influenza 

Introduction 

Chip Walter, MD 

Chair, Influenza Work Group 

Dr. Walter reported that since the June 2016 ACIP meeting, the 2016-2017 ACIP Influenza 

Statement was published in the MMWR August 26, 2016. In addition, there were two new 

licensures: 

 AFLURIA® Quadrivalent manufactured by SeqirusTM, which is a quadrivalent inactivated 

influenza vaccine (IIV) on August 26, 2016 

 FLUBLOK® Quadrivalent manufactured by Protein Sciences Corporation, which is a 

quadrivalent recombinant influenza vaccine, on October 7, 2016 

He indicated that the topics for this session would focus on an influenza surveillance update and 

AFLURIA® Quadrivalent vaccine. As a reminder, there was a discussion during the February 

2016 ACIP meeting on FLUBLOK® Quadrivalent. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Epidemiology / Surveillance Update 

Lynette Brammer, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

During this session, Ms. Brammer provided updates on international influenza activity, recent 

US influenza activity, and the Southern Hemisphere vaccine recommendations recently made. 

Regarding influenza activity for the last year in the Northern Hemisphere, influenza 

A(H1N1)pdm09 predominated along with some influenza B viruses and some H3N2 activity 

toward the end of the season. Currently, Northern Hemisphere activities are very low. The 

Southern Hemisphere’s season started out predominated by H1N1 viruses, with an increase in 

H3N2 viruses toward the end of the season. Looking at the Southern Hemisphere and a few 

representative countries, Australia contributed a large proportion of the late season H3N2 

viruses. That actually was their predominant virus for that season. South Africa had an 

interesting season. They started out as influenza-B predominant, went into an H3 predominant 

period, and then had a third wave of influenza activity during which H1N1 viruses predominated. 

Argentina and Chile are representative of what occurred in South America, with both having 

H1N1 predominant seasons with some influenza B activity. 

In terms of recent activity in the US, 1.7% of specimens tested for influenza were positive for 

influenza at week 40 compared to the 24% seen at peak last season. Based on results from 

public health laboratories, recent influenza activity was low relative to what would be seen at 

peak. Influenza B viruses predominated going into the summer, but influenza A(H3N2) viruses 

became more frequently detected and predominated at about 90% by October. The public 

health laboratories submitted a subset of their influenza positives to CDC for genetic and 

antigenic characterization. Over the summer, 52% of the viruses reported by public health 

laboratories were H3N2 viruses. Among those that CDC was able to characterize genetically, 

there are three genetic groups among the H3s currently: 1) 3C.3a, which last year’s 

A/Switzerland vaccine component represented; 2) 3C.2a, which is this year’s H3N2 component 

A/Hong Kong/4801; and 3) 3C.2a1. From May 22, 2015 through October 8, 2016, 27% of the 

H3N2 viruses have been 3C.2a viruses, 34% have been 3c.2a1 viruses, and 39% have been 

3C.3a viruses. Although there are multiple genetic groups among the H1 viruses, all of the ones 

detected in the US have been 6B.1 viruses. There is not a lot of diversity among either lineage 

of the influenza B viruses. 

Looking at the genetic data on an international level just to put things into context, 3C.2a and 

3C.2a1 predominated in most areas of the world. In North America, there were 3C.3a viruses at 

the end of the season last year. Those viruses seemed to be decreasing in prevalence, and 

North America was really the only one to see that level of 3C.3a viruses circulating. Of the 

A(H1N1)pdm09 viruses, there are 6B, 6B.1, and 6B.2 genetic groups. Almost all viruses 

worldwide are 6B.1 at this point, although 6B.2 viruses were being seen in Asia and Oceania. 

Antigenically, all 8 of the A(H1N1)pdm09 viruses characterized from the US over the summer 

are similar to the A/California/7/2009-like vaccine component. Among the 53 A(H3N2 viruses, 

44 (83%) are antigenically similar to the A/Hong Kong/4801/2014-like, the 3C.2a genetic group 

in this year’s vaccine for the US. Some of those are low reactors. Among the viruses that 

reacted poorly with ferret antisera raised against A/Hong Kong/4801/2014-like viruses, 8 of 9 

(90%) are more closely related to A/Switzerland/9715293/2013 (genetic group 3C.3a). Among 

the influenza B viruses, all 26 B/Victoria-lineage viruses were antigenically characterized as 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

B/Brisbane/60/2008-like, which is the influenza B component of the 2016-2017 Northern 

Hemisphere trivalent and quadrivalent influenza vaccines. All 33 B/Yamagata-lineage viruses 

were antigenically characterized using ferret post-infection antisera as B/Phuket/3073/2013-like, 

the influenza B component of the 2016-2017 Northern Hemisphere quadrivalent influenza 

vaccines. 

In terms of geographic spread as of Week 40 in the US, 36 states and the Virgin Islands had 

sporadic activity. One state, New Hampshire, experienced local activity. Regarding outpatient 

visits for influenza-like illness (ILI) during the same week, 1.1% of outpatient visits were for ILI. 

This is what would be expected at this time of year compared to other recent seasons. There is 

no difference by state in that no states are experiencing more activity, with all states currently at 

minimal influenza activity. The percent of death certificates that have any mention of 

pneumonia or influenza is low at 5.4% for deaths that occurred for the week ending September 

24, 2016 compared to the baseline of 6.3%. That is probably somewhat lower than what the 

final percentage will be, but there is no reason to believe that any influenza-associated mortality 

is being observed at this point. 

The recommendation for 2017 Southern Hemisphere trivalent influenza vaccine components is 

as follows: 

 A/Michigan/45/2015 (H1N1)pdm09-like virus 

 A/Hong Kong/4801/2014 (H3N2)-like virus; and 

 B/Brisbane/60/2008-like virus. 

The recommendation for 2017 Southern Hemisphere quadrivalent influenza vaccine 

components are as follows: 

 A/Michigan/45/2015 (H1N1)pdm09-like virus 

 A/Hong Kong/4801/2014 (H3N2)-like virus 

 B/Brisbane/60/2008-like virus 

 A B/Phuket/3073/2013-like virus 

In summary, influenza A(H1N1)pdm09, A(H3N2), and both lineages of influenza B viruses 

continue to circulate worldwide. Activity in the US and other Northern Hemisphere countries 

remains low at this time. The recommended components for the 2017 Southern Hemisphere 

vaccine includes an updated H1N1 virus, which is the first change in the H1 component since 

the 2009 pandemic. Global laboratory data continue to indicate that most currently circulating 

viruses are antigenically similar to the vaccine viruses included in the 2016-2017 US vaccines. 

This suggests that vaccination with Northern Hemisphere influenza vaccine should offer 

protection against the majority of circulating viruses analyzed to date. 

Discussion Points 

Dr. Belongia asked whether there had been any antigenic characterization of the 3C.2a1 

viruses. 

Ms. Brammer replied that from what she understood, the 3C.2a1 viruses are antigenically very 

similar to the 2As. 

Ms. Stinchfield (NAPNAP) inquired as to whether there was any indication of severity of the 

different genetic subgroups that would allow for predictive work. 

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The FDA approved AFLURIA® trivalent influenza vaccine (TIV) for use in individuals ≥ 18 years 

of age in November 2007. AFLURIA® TIV was approved for use in individuals ≥ 5 to 18 years of 

age in December 2011. In August 2016, AFLURIA® quadrivalent influenza vaccine (QIV) was 

approved for use in individuals ≥ 18 years of age. The current ACIP recommendation for 

AFLURIA® is for use in individuals ≥ 9 years of age. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Ms. Brammer responded that at this time, there were no data to indicate that the severity of any 

of these viruses would be different from what is typically observed with influenza viruses. 

AFLURIA® Quadrivalent Influenza Vaccine 

Gregg C. Sylvester, MD, MPH 

Head of Medical Affairs 

SeqirusTM A CSL Company 

During this session, Dr. Sylvester presented the pivotal Phase 3 trial that led to the US approval 

of the AFLURIA® Quadrivalent Influenza Vaccine in adults 18 years of age and older. As a 

reminder, influenza is a highly infectious respiratory infection1. Seasonal epidemics occur 

predominantly during winter, with an annual incidence of 5% to 10% in adults2. Infection is 

associated with significant morbidity and mortality, with an estimated 250,000 to 500,000 deaths 

directly attributed to influenza annually worldwide2. Conventionally, influenza vaccines are 

trivalent, consisting of two influenza A subtypes and one influenza B lineage. However, two 

antigenically distinct B lineages co-circulate from year-to-year3. Predicting which B will 

predominate during the season can be problematic. Thus, the quadrivalent vaccines have been 

developed comprised of the 3 strains contained in the trivalent plus the additional B strain 

[

1Bouvier NM, Palese P. Vaccine. 2008;26 Suppl 4:D49-53; 2World Health Organisation. 

Influenza. factsheets/fs211/en/. 13 July, 2016; 3Beran J, Wertzova V, Honegr K, Kaliskova E, 

Havlickova M, Havlik J, et al. BMC Infect Dis. 2009;9:2]. 

AFLURIA® is licensed in the US as a trivalent and quadrivalent vaccine. It is an egg-derived, 

purified, inactivated, split virion influenza vaccine. It is manufactured in Parkville, Australia. 

There are two vaccine formulations: 

 0.5mL pre-filled syringe, thimerosal-free 

 5mL multi-dose vial, thimerosal-containing 

In terms of the Phase 3 adult QIV study, SeqirusTM is taking a stepwise approach to its 

quadrivalent clinical development program. The study for children ≥5 to <18 years of age is 

completed and will soon be submitted to the FDA. The QIV pediatric study among children 6 

months to <5 years of age is underway, and the last Dr. Sylvester heard, about 300 participants 

were enrolled in that study. 

Here is the clinical trial algorithm for the adult study, which was conducted in the US in 31 

centers during the 2014-2015 Northern Hemisphere influenza season: 

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A total of 3484 participants were randomized into 3 groups in a 2:1:1 ratio. The vaccine group 

included 1741 participants, the AFLURIA® TIV B/Yamagata group had 871 participants, and the 

AFLURIA® TIV B/Victoria group had 872 participants. The demographics of the participants 

were well-balanced between groups. The mean age was 58 years, with a +/- of 18 years. The 

age groups were stratified, with half of them below 65 years of age and the other half 65 years 

of age and above. There were slightly more females than males, and the majority of the study 

participants were white. Nearly two-thirds of the study participants received an influenza 

vaccine in the prior year. 

 

Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

Healthy men and women ≥18 years of age who resided in the US were enrolled in the study. 

The exclusion criteria were: 

 Allergic to egg proteins or any study vaccine component 

 Acutely ill 

 Immunocompromised 

 Influenza vaccine within the preceding 6 months or any licensed vaccine within 14 days for 

inactivated vaccines or 28 days for live vaccines 

 Immunoglobulins or blood products within the last 3 months 

 Investigational product within the last 28 days 

 Anticoagulant therapy, except antiplatelet agents 

 History of Guillain-Barre Syndrome (DBS) or demyelinating disease 

 History of drug or alcohol abuse 

 Clinically significant disease in the investigator’s opinion 

The primary objective of the study was to compare the QIV to a US licensed seasonal vaccine, 

AFLURIA® TIV. A non-inferiority immunogenicity design was used with eight co-primary 

endpoints (2 endpoints, 4 viral strains). GMTs and seroconversion rates (SCRs) were analyzed 

for the 4 viral strains. These endpoints were defined in accordance with the FDA criteria for 

non-inferiority studies. For GMTs, the upper bound of the 95% confidence interval of the GMT 

ratios was not to exceed 1.5. For SCRs, the upper bound of the 95% confidence interval of the 

difference for the SCRs was to be ≤ 10%. If all 8 co-primary endpoints meet the pre-specified 

FDA criteria, then non-inferiority for the QIV compared to the TIV can be concluded. 

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For secondary endpoints, the same non-inferiority criteria were applied in each age group 18 to 

64 years and ≥65 years. Superiority was assessed for the unmatched B strain included in the 

QIV, but not in the respective TIVs overall and in each age group (18 to 64 years and ≥ 65 

years). This allowed them to use the FDA superior criteria which states that for the GMTs, the 

lower bound of the 95% confidence interval of the GMT ratio should be greater than 1 and the 

lower bound of the 95% confidence interval of the SCR differences should be greater than 0%. 

If these two criteria are met, superiority can be concluded for the alternative lineage B strain. 

Regarding the results, the ratios for GMTs were similar between vaccines in the entire age 

group. The pre-specified non-inferior criterion for the ratio of GMT was met for all 4 strains. 

The ratio for GMTs were similar for each of the age groups. SCR also were similar between 

QIV and each TIV comparator for the matched strains. The pre-specified non-inferiority criterion 

for the SCR difference was met for all 4 strains, as well as for each age cohort. The 

immunological superiority of the unmatched B strain was demonstrated for both B strains in the 

QIV when comparing the ratio of GMTs to each TIV in which the strain was absent. The 

superiority criterion also was met for the B strains contained in the QIV when analyzing the 

difference in SCRs for all participants 18 years of age and above, and for each age cohort. 

All three vaccines were well-tolerated. The safety profile for the QIV was similar to that of the 

TIV comparators. Over half of the participants reported an AE during the study. The majority of 

those AEs were classified as Grade 1, meaning symptoms that are easily tolerated and do not 

interfere with normal everyday activity. No participants left the study due to an AE. The most 

common solicited local AE in all three groups was pain at the site of injection at 36.5% overall. 

The percentage of vaccine-related unsolicited AEs was slightly higher in the QIV group. There 

were 4 SAEs in 3 patients, which were assessed by the investigators as being related to QIV. 

One was asthma 2.5 weeks after the vaccine, one was acute pancreatitis 1 week later, one was 

hypoxia 10 days later, and one was pneumonia 4 days after receipt of the vaccine. Similar 

frequency and intensity were seen in all three vaccine groups, with the vast majority in the 

Grade 1 category. As mentioned earlier, pain at the site of injection was the most common local 

reaction. Myalgia and headaches were most commonly reported as systemic. 

In terms of the strengths of the study, the trial design was prospective, double-blinded, and 

randomized. It was a Phase 3 with active-control, and it was a multicenter study in 31 centers in 

the US. The study was sufficiently powered to meet the primary endpoints. However, there are 

potential limitations. The use of immunogenicity as a surrogate for protection may not be a true 

representation of clinical efficacy. In addition, participants with moderate to severe acute 

illnesses were excluded from the trial. 

In summary, AFLURIA® Quadrivalent Influenza Vaccine met non-inferior immunogenicity for all 

strains to both comparator TIVs in adults ≥18 years of age and in each age group 18 to 64 years 

and ≥ 65 years. Immunologic superiority of the alternate B strain (B/Yamagata and B/Victoria 

strain) was also met for both of the age cohorts by the GMT ratios and SCR for each virus 

strain. The vaccine safety profile was found to be acceptable. FDA approval was granted on 

August 24, 2016. 

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Discussion Points 

Ms. Pellegrini noted that the study population had a very low percentage of minority participants 

despite the fact that it was conducted in 31 centers. 

Dr. Sylvester replied that the study population was 82% white. As they heard the previous day, 

all industry is trying to do a better job of increasing the diversity within clinical trials. As they 

assess the population of under 6 to 59 months of age, they certainly will take that into 

consideration. 

Dr. Messonnier requested that Dr. Sylvester discuss vaccine supply for this and next year. 

Dr. Sylvester responded that both the QIV and TIV formulations are available in the US this 

year, and plan to do the same next year. He called on one of his colleagues to provide further 

details. 

Aaron Rak (SeqirusTM) added that because the QIV formulation was just licensed in August, the 

vast majority of the doses coming in are trivalent, although there has been a lot release of QIV. 

Next year, the plan is to have a mix of both QIV and TIV in addition to Seqirus’sTM other 

licensed vaccines. 

Dr. Belongia requested information on the relative price increase from the TIV to the QIV. 

Aaron Rak (SeqirusTM) replied that the list price for the TIV prefilled syringe is $14.92, and the 

list price for the QIV prefilled syringe is $16.61. That is a $1.70 increase for the prefilled 

syringe. They will bring in both formulations next year (prefilled and multi-dose vials), currently 

only the prefilled syringe is available. 

Respiratory Syncytial Virus Vaccine 

Introduction 

Robert Atmar, MD 

Baylor College of Medicine 

Chair, ACIP RSV Vaccines Working Group 

Dr. Atmar reminded everyone that the ACIP Respiratory Syncytial Virus (RSV) Vaccines WG 

was convened to evaluate vaccine use in adults ≥60 years of age and in adults with underlying 

medical conditions. This was in anticipation of results of a vaccine product that is in Phase 3 

clinical trials. The RSV session during the June 2016 ACIP meeting focused on providing an 

overview of RSV and RSV vaccine development, including targeted vaccine populations. On 

September 15, 2016, top-line results from the NOVAVAX RSV F Vaccine Phase 3 clinical trial 

were released. This is a snapshot of RSV vaccine development: 

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This session included an update on the burden of RSV disease in older adults, as well as an 

update on NOVAVAX RSV vaccine development programs. 

The next steps for the RSV Vaccines WG are to: 1) continue to review RSV vaccine product 

clinical trial data in targeted populations as they become available for older adults, pregnant 

women, and infants and young children; and 2) present to ACIP when new updates in RSV 

epidemiology and clinical trial data occur. 

Burden of Disease in Older Adults 

Ann R. Falsey, M.D. 

University of Rochester 

Dr. Falsey pointed out that people stop thinking about RSV when they leave medical school if 

they do not go into pediatrics. With that in mind, she gave an overview of the studies that 

suggest that RSV has a significant burden of disease in adults. First, she shared some history 

and basics. 

In 1956, Morris described an outbreak of respiratory illness in a chimpanzee colony at Walter 

Reed. The cytopathic agent isolated from a chimp named Sue was called CCA, for chimpanzee 

coryza agent. The following winter, Dr. Robert Chanock recovered a similar virus from infants 

hospitalized with lower respiratory tract symptoms, and the virus was very sensibly renamed 

Respiratory Syncytial Virus (RSV) to reflect the giant syncytia seen in culture. For the past 40 

years, the epidemiology of RSV has been exhaustively studied in infants and young children, in 

whom it is the single most important respiratory pathogen in the first year of life. It has been 

linked to 90,000 to 100,000 annual hospital admissions in the US and approximately 300 to 500 

deaths. In 1966, there was a formalin inactivated vaccine trial that was a disaster. It resulted in 

enhanced disease, such that infants who got the vaccine had higher rates of hospitalization and 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

even some deaths. Needless to say, vaccine development has been very slow and cautious 

ever since and there still is not a vaccine for either children or adults. 

It was not until the 1980s that RSV was appreciated as a potential pathogen in adults. Before 

launching into the clinical descriptions, Dr. Falsey quickly reviewed a few relevant points about 

the virus structure. There are 10 genes that encode for 11 proteins. It is a single-stranded RNA 

virus with 8 structural proteins. There are two major surface glycoproteins, the F or fusion 

protein and the G which serves as the attachment protein, both of which induce neutralizing 

antibodies. The G protein has a fair amount of antigenic diversity and defines group A and B 

viruses. In contrast, the F protein is relatively well-conserved among RSV isolates and 

therefore has been identified as an important component of candidate vaccines. RSV is not like 

influenza in that it does not undergo major antigenic shift and drift, but it is likely that antigenic 

diversity plays some role in adult reinfection, but it is really not clear how much. 

There is a variety of evidence that looks at RSV disease. Initially, most of the reports were just 

case reports or outbreaks, which were primarily in nursing homes. There is a body of indirect 

evidence that uses modeling studies. There are some illness-based studies that look at people 

presenting for medical care either to their general practitioner, the emergency department (ED), 

or the hospital. There are prospective studies following groups of people for respiratory illness, 

which are the most difficult and expensive to conduct. 

As mentioned, RSV came to the medical community’s attention when outbreaks started to be 

described in nursing homes. In these situations with closed populations, the attack rates can be 

quite high, up to 89%. Looking at prospective studies in nursing homes, the incidence of RSV 

can vary from 1% to 15%. Generally, it is considered a nosocomial infection that either the staff 

or family members are bringing into the facility. The reported severity in nursing home patients 

is highly variable, with reports of pneumonia ranging from 0% to 55% and reports of deaths 

ranging from 0% to 53%. Part of that probably is the population in a specific nursing facility. 

Some facilities have healthy older people who are only somewhat dependent, while others have 

very frail residents. 

Only about 5% of older people reside in institutions, with 95% of older people living in the 

community. One of the first studies that examined community-dwelling elderly was conducted 

by Scott Dowell in which he looked at lower respiratory tract infections in hospitalized adults. 

Using serology, he found that RSV was third right after pneumococcus and influenza A and B as 

a cause of respiratory illness, in this study conducted over 2 winters with almost 1200 

participants. 

As a lead in to the modeling studies, Dr. Falsey shared the following formula emphasizing that 

modeling is an important way to predict disease burden: 

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Modelers basically correlate culture data and viral activity with events in other populations. The 

first and one of the best studies looking at RSV in all ages correlated viral activity with national 

death data for the time period 1976-1997, looking at deaths due to pneumonia, influenza, 

circulatory, and respiratory illness. They found that while flu dominated over RSV, what took 

everybody by surprise was that in the adult age groups, there were nearly 11,000 RSV deaths 

amongst older adults. This was not previously well-appreciated. Compared to influenza, it is 

about two-thirds to about half of influenza. This was one of the first assessments that 

suggested that maybe RSV is not like influenza in an older adult, but it is not insignificant either 

[Thompson et al JAMA 2003]. This approach was then used again to assess the next 20 years 

from 1997-2009. Using a very similar analysis to Thompson’s, this group from GSK got very 

similar results looking at adult deaths in the US. These two studies looked at 40 years of data 

[Matias et al IORV 2014]. 

Douglas Fleming is from the UK and he has been looking at RSV in older adults for the last 20 

years using modeling studies as well. In a very recent publication, he showed that influenza 

burden tends to go up and down over time. That may be because when there are major H3N2 

years, a lot of excess deaths are observed among older people. However, RSV is more 

monotonous. Fleming then looked further and broke it down by age groups of 18 through 49, 50 

through 64, 65 through 74, and over 75. This revealed that the greatest increase occurred in 

people over 75 years of age, and there was some increase in people 65 through 74 years of 

age. It is important to note that the population of people over 80, which geriatricians refer to as 

the old old, is growing significantly in most developed nations [Fleming DM et al BMC 2015]. 

Dr. Falsey pointed out that before moving into a discussion of studies looking at disease burden, 

it is important to understand diagnosis because the way RSV is diagnosed will alter the results 

of studies assessing disease burden. Children produce a lot of mucous. An infant with a 

primary infection has a great deal of virus in their respiratory secretions, and this produces a 

characteristic clinical symptom of bronchiolitis. So, it is not so hard to make the diagnosis in 

young children. When she began studying the virus, the tools available were viral culture and 

serology. Viral culture is very insensitive for making the diagnosis. RSV is more labile than 

influenza. It does not survive transit. There is not that much in secretions, and it would take a 

while for the virus to grow. While serology is good, it is necessary to have convalescent 

serology. The patient has to survive to be able to get that, and it also has to be well-timed. 

When the advent of PCR came along, it was anticipated to be able to solve all of the problems. 

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PCR has revolutionized the understanding of many viruses, because it allows them to be 

detected in many ways that could not be done before. 

There are a number of diagnostic challenges in older adults. Unlike children, they lack 

distinctive syndromes (croup, bronchiolitis). Older people have a diminished febrile response. 

A lot of the studies looking at RSV are tag-on studies to influenza studies in which the case 

definition is ILI, which includes fever. The presence of a respiratory infection sometimes may be 

completely overshadowed by exacerbations of comorbid diseases when these individuals 

present to the hospital. They may be having a chronic obstructive pulmonary disease (COPD) 

or heart failure exacerbation, and so no one thinks about the fact that it all started with a virus. 

One of the most important things is that most people just do not even consider the diagnosis of 

RSV when an adult is admitted to the hospital. In addition, adults shed lower titers of virus for a 

shorter period of time in the nose than infants. 

Based on some data from an epidemiologic study that the University of Rochester conducted 

using viral culture, PCR, and serology to define infection, it was not very surprising that in the 

study population, culture was not very sensitive, as it only detected 4.1%. PCR was a 

significant jump at 9%. Serology yielded the highest number of people with infection at 12.4%. 

Everybody had a PCR in that study, but not everybody had serology because they did not return 

or they died. Of the participants, 1,114 people had all of the tests available. A substantial 

proportion, 37, were positive by all three tests and an equal number were positive by PCR and 

serology, which is no surprise. Nobody was culture positive and PCR negative. It is worth 

pointing out that out of the 117 people with RSV, 30 people were serologically positive only and 

had negative PCR and culture. If just using PCR, those people would have been missed. That 

is not to say that serology is perfect, because 13 people were either PCR or culture positive and 

serologically negative. 

If there is very well-timed serology in a prospective study; that is, there is a baseline antibody 

level and then good tight acute and convalescent serology, almost all older people do have a 4­

fold serological response. The reason that serology sometimes is not so great is because if 

people are being evaluated at the time they present for medical attention, they usually are 5 to 6 

days into their illness. In all adults, RSV is a reinfection so everybody has baseline immunity 

and they have a fairly rapid amnestic response. Antibody starts to rise around day 3 and by the 

time the patient presents at day 5 or 6, they have already had a 2-fold rise in antibody. So the 

rise in antibody might be missed in people presenting to the hospital because nobody goes in 

with a runny nose. In the typical RSV illness, the patient gets a cold. They have a runny nose 

for a few days. They then begin to get wheezy. Then they get more short of breath. It really 

takes 5 or 6 days for them to decide that they need to see a doctor. 

In terms of the location of the sample, as the illness progresses, it may be that the virus is no 

longer in the upper airway and has moved down to the lower airways. When thinking about viral 

testing, people always think about the swab up the nose and really do not think about testing 

sputum. Angela Branch at the University of Rochester conducted a study in which she 

assessed the improved diagnostic yield by combining sputum and nasal swab testing. It was 

not specific to RSV, but 63 people were RSV positive and 22% were positive only in their 

sputum. Nasal swab positive only was mostly because they did not have a sputum. They could 

not cough it up. One of the issues with sputum is that not everyone can raise a sample. 

However, if it can be collected, it can add to the diagnosis, particularly if someone has been sick 

for a while [Branche et al JMC 2014]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

To summarize the sensitivity of RT-PCR and serology, the timing of samples is important for 

both PCR and serology. Early in illness, in the first couple of days, a nasal swab for PCR is 

very sensitive. Later in illness PCR may be negative, but sputum may be of value. Well-timed 

serology is very sensitive in older adults. However, the rapid amnestic response may obscure 

antibody rises in people presenting for medical attention 5 to 6 days into illness. The sensitivity 

of diagnostic methods in the elderly varies widely. Standard culture is 5% to 40% sensitive, but 

only in a research institution where someone runs right to the laboratory with the cultures. It is 

still not a great way to make the diagnosis. The rapid antigen tests with 0% to 24% sensitivity 

are next to worthless and they are not recommended. PCR (75% to 82% sensitive) and 

serology (85% to 90% sensitive) are the best ways to make the diagnosis. Obviously, in a 

clinical scenario, only PCR is needed. But when thinking about vaccine and epidemiologic 

studies, these two tests are complementary and each have an advantage. 

One of the major problems with RSV is that it has an identity crisis. Looking at the discharge 

medical record of a women who was diagnosed with RSV, she presented with congestion, 

difficulty breathing, poor appetite, and dehydration. She eventually went into respiratory failure, 

was intubated, required dialysis, had a gastrointestinal (GI) bleed, and then died. She had a 

PCR that was positive for RSV and an illness that was fairly characteristic at the onset. But her 

ICD-10 discharge diagnoses were hypotension, hyperkalemia, dehydration, diabetes mellitus, 

and chronic kidney disease (CKD). Nowhere in there was RSV. Dr. Falsey said she would 

propose that none of these other things would have happened had she not had RSV and it 

began a cascade of bad outcomes. 

Dr. Falsey presented some data from a study that she and Dr. Edward Walsh conducted a 

number of years ago. This was a prospective diagnosis-based study conducted for 4 winter 

seasons between 1999 and 2003. They conducted prospective surveillance of healthy older 

people living in the community and adults with underlying cardiorespiratory disease in the 

community. At the same time the prospective evaluations were being done, they evaluated 

adults who were hospitalized at their institution with acute cardiopulmonary conditions, with the 

exception of an acute myocardial infarction (MI). To diagnose RSV, they used culture, one tube 

nested RT-PCR, and serology. At this point, it was new that thought was being given to 

developing vaccines and drugs for RSV. Everybody would agree that influenza is a major 

problem in the elderly, so they used influenza as a yardstick. They enrolled over 600 healthy 

elderly and over 500 high-risk and evaluated nearly 1500 illnesses in the hospital over the 4 

years. 

Regarding the incidence data in the prospective group, RSV ranged from 3.2 in a low year to 

7.6 in a high year, with an average of 5.5 infections per 100 per season. That was about twice 

as common as influenza A, which was 2.1. It is important to point out that this is a heavily 

vaccinated population. These numbers would likely look very different if there was not influenza 

vaccination. It is also important to point out that this is infection, not only symptomatic 

infections. Among both the influenza and RSV patients, 10% had asymptomatic serological 

rises from baseline to the end of season. It is not clear whether these people had illnesses they 

did not report because they were mild illnesses, or if they were truly asymptomatic. Most of 

these individuals, 90%, had symptomatic illnesses that were evaluated. 

Also important to address in older adults is functional impact. To assess this, they looked at 

whether the patients were housebound, bedbound, or unable to do their activities of daily living 

at any point during their illness. Influenza had a greater effect on the healthy elderly, but it is 

important to point out that 39% of the healthy elderly could not do their activities of daily living 

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when they were sick. In the high-risk patients, the influenza and RSV differences were less 

dramatic and there was a more functional impact. 

In terms of utilization of healthcare resources, in the high-risk group, there were 54 infections, 

16% were hospitalized, and 5% died. While the healthy older persons might have felt terrible 

and might have gone to see their doctors, nobody was hospitalized and nobody died. The 

medically attended rates of illness in the healthy group varied between 0.50 - 1.20 / 100 

depending on the year. For the high-risk group, it was about double at 1.8 - 4.4 / 100. Using 

the population of Rochester, the investigators estimated a hospitalization rate of about 1 / 1000. 

With regard to admissions due to RSV and influenza, there was a dramatic seesawing for 

influenza because year 1 and year 3 were big H3N2 years. RSV was somewhat steadier. Over 

the 4 years, RSV accounted for 9.0% of the wintertime hospitalizations due to cardiopulmonary 

diseases and influenza A accounted for 9.5%. The characteristics of those presenting with RSV 

and influenza were very much the same. The mean age was 76 and there were very high rates 

of underlying heart and lung disease. The people who are hospitalized are not the healthy older 

adults, with the exception of the old old. 

With big groups of people with RSV and influenza, it is possible to get nice p-values and find 

that there is more nasal congestion, dyspnea, and wheezing among those with RSV; whereas, 

influenza patients have higher rates of fever. However, it is not possible to tell the difference on 

an individual basis. A case-based definition cannot be developed that provides any kind of 

discriminatory ability. It is necessary to perform a test, and studies require a laboratory 

component. In terms of outcomes in the hospitalized subjects, rates of pneumonia, intensive 

care use, ventilator support, and death rates were nearly identical. Once someone is frail 

enough to end up in the hospital with either one of these viruses, the outcomes are very similar. 

Falsey et al estimated that about 177,000 people would be hospitalized and there would be 

about 14,000 deaths in the US. Thompson estimated 11,000 using modeling. So, they felt very 

good that these were pretty close using very different methodologies. Therefore, she does 

believe that is roughly the attributable mortality each year [Falsey et al NEJM 2005;352:1749]. 

There is nothing unique about the extremely long, cold, dreary, snowy Rochester weather. In 

2012, Dr. Keipp Talbot and her group at Vanderbilt used only PCR and estimated that 6.1% of 

their wintertime hospitalizations were due to RSV. If the serological results were added, this 

would be very similar to the Rochester data. They did some estimates using the population of 

Davidson County and calculated a hospitalization rate of 1.5 / 1000. So again, in a different 

geographic location, this team came up with similar data [Widmer et al JID 2012]. 

Dr. Edward Belongia and colleagues at Marshfield Clinic conducted some studies in conjunction 

with influenza vaccine efficacy studies to assess influenza vaccine efficacy using a test-negative 

case design. They had periods of surveillance when influenza was very active. RSV activity is 

usually just a broader base, so they were missing some of the times that RSV was active and 

needed to fill in with some modeling in addition to specific viral testing. They used PCR to do 

testing. Their estimate of medically attended respiratory illness in adults ≥50 was 1.54 / 100 

[McClure et al Plos One July 2014 ;9:e1025]. 

One of the questions sometimes pertains to how variable RSV is in a season in adults in terms 

of mild versus bad years, so Dr. Falsey put together some of the Rochester data from the 

prospective cohort studies to illustrate the variability because they have been conducting these 

studies for a long time. The low one year was 2.5 and the high year that was a banner year 

among their COPD patients was 10.7. It is variable, so investigators may have the misfortune to 

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conduct a vaccine study in a low year. Looking at illness-based data, there was a low of 4% of 

the respiratory illnesses being RSV and a high in another study of 13%. 

A number of studies are being conducted throughout the world. It is important when evaluating 

other studies to look at the way they diagnosed the infection. Van de Hoogen in the 

Netherlands, who is a superb virologist, found 0 RSV infection. The diagnostic methodology 

used was serology and culture. Culture is insensitive, but it would seem that some serological 

infections would have been picked up. A German study found 25% RSV infection rates using 

purely PCR. That is so high that it may suggest something about the specificity of the PCR or 

whether there was contamination of results. There are a lot of studies being conducted in many 

countries around the world that typically use a multiplex PCR that generally has 15 targets. It is 

important to remember that when a test is optimized for 15 different targets, it is going to lose 

some sensitivity for a specific target. But these data coming from around the world report a low 

of <1% RSV to a high of 7%. It is always important to remember with these studies to 

determine whether they were conducted over an entire year, in which the incidence would be 

lower, or if they focused on the winter season. 

Turning to some data from China, Dr. Falsey noted that Nelson Lee has been conducting some 

very good influenza work. He works in Hong Kong and has more recently turned his attention to 

RSV and has some interesting data coming from Hong Kong. In a 3-year study, he and his 

team identified 607 adults hospitalized with RSV at the same time that there were 547 with 

influenza A. The mean age was almost identical to the other side of the world in Rochester 

where it was 76. They also found that those who were hospitalized had a lot of chronic medical 

conditions. One thing that differed was the fact the people in Hong Kong seemed to go to the 

hospital quicker than people in the US. Influenza patients present earlier than RSV patients. A 

high fever in an older adult is likely to drive them to medical attention more quickly than the 

runny nose that evolves into shortness of breath [Nelson Lee et al CID 2013;57 1069]. 

One thing that is not known is the complication rate—the downstream problems that result from 

RSV. Dr. Falsey believes there are plenty, but it is just not well-understood at this point. This 

would include functional decline, bacterial complications, and cardiovascular events. This is 

clear with influenza. In large influenza epidemics, there is a clear spike in heart attacks and 

strokes, but this is not clear with RSV. Dr. Falsey and her colleagues conducted a study 

recently to assess the issue of bacterial complications with viral infections. It is much talked 

about, and clearly there is a relationship between viral infection and bacterial superinfection. 

However, it is very hard to diagnose a bacterial infection with any specificity and sensitivity. In 

this 3-year study, they evaluated people presenting with respiratory illness. In addition to 

comprehensive viral and bacterial testing, they did a serum biomarker of procalcitonin. 

Procalcitonin is high in people with bacterial infections and normal in viral infections. By 

combining traditional bacteriology with high procalcitonin, they found that 31% of RSV patients 

admitted to the hospital had some evidence of a bacterial infection. There did not seem to be 

any major differences between the common respiratory viruses [Falsey et al JID 2013]. 

While Dr. Falsey said she could find almost nothing on cardiovascular complications in RSV, 

she did find a study from Volling in Toronto. This was an observational study in which 22% of 

their RSV patients who were admitted had some type of cardiovascular complication [Volling 

BMC 2104]. 

To summarize the rates that the evidence provides, infection ranges from 2 to 6 per 100 per 

season, medically attended disease from 0.5 to 4 per 100, hospitalization from 1 to 1.5 per 

1000, and death rates from 0.4 to 7 per 10,000. Secondary complications are unknown. 

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Discussion Points 

Dr. Atmar said he was interested in Dr. Falsey’s thoughts on the use of serology in vaccine 

studies. For example, they found with influenza that vaccinees are less likely to have serologic 

responses than are non-vaccinees, which can bias in favor of vaccine efficacy. He asked 

whether she anticipated that this could be a problem using that diagnostic method in the 

evaluation of vaccine efficacy or effectiveness. 

Dr. Falsey replied that she did not think an antigen could be used that is in the vaccine. Most of 

the RSV vaccines in development are based on the fusion protein, so another purified antigen 

could be used, the attachment protein could be used, the nuclear protein could be used—it 

would just be important to eliminate whatever antigen happens to be in the vaccine. 

Dr. Hahn (CSTE) asked whether anything was known on the source of infection in elderly. For 

example, are caregivers of young children at higher risk of becoming hospitalized with RSV? 

Dr. Falsey replied that it is certainly sensible to think that young children are the origin. RSV 

exposure during the winter is probably fairly prevalent, even if not exposed to young children. 

They have assessed exposure to children as a risk factor for infection, and have found that it is 

a factor. However, it is not an overwhelming factor. They recently conducted a study with 

MedImmune to examine whether there was any group who could be at really high-risk. They 

enrolled people who had regular exposure to school-aged children and underlying heart and 

lung disease, and found that the rate of infection in that group was almost 14%. 

Evan Anderson (Emory) noted that several groups have now described cross-reactive 

antibodies between RSV and human metapneumovirus (hMPV). He asked whether she had 

seen any evidence in her data of RSV serologic conversion due to a recent hMPV infection. 

Dr. Falsey indicated that in the large epidemiologic study, they did do serology for 

metapneumovirus and did not find that it was an issue. They were very distinct. 

Update on NOVAVAX RSV Vaccine Development Programs 

Dr. Jeffrey Stoddard 

Vice President Medical Affairs 

Novavax, Inc. 

Dr. Stoddard shared a high-level company overview indicating that they have a proprietary 

vaccine technology platform that involves baculovirus (BV) transfection of and Spodoptera 

frugiperda (Sf9) insect cell line for the production of recombinant immunogenic nanoparticles. 

They have 5 facilities, including Gaithersburg and Rockville, Maryland and Uppsala, Sweden. 

There is a high degree of experience across their management team, and the development and 

commercialization infrastructure necessary to bring products to market. They have commercial 

grade GMP manufacturing capacity, a strong balance sheet, and substantial funding support 

from the Bill & Melinda Gates Foundation for maternal programs. 

In terms of Novavax’s history of leadership in RSV vaccine development, they have achieved 

several milestones. Their Vice President of Preclinical Vaccine Research, Gale Smith, was the 

original discoverer in the early 1980s of the Sf9 insect cell line that could grow and produce 

recombinant protein nanoparticles based on transfection with the BV. The company’s work in 

RSV vaccine development dates back to about 2009, for which they have reached a number of 

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To summarize the Phase 2 trial, it was well-tolerated and had an acceptable safety profile. It 

was the largest ever prospective study of the RSV attack rate in community dwelling older 

adults. Of the older adults in the placebo group, 4.9% had symptomatic RSV and 88% of these 

illnesses were associated with LRTI. In terms of immunogenicity and efficacy, there were 

robust and specific anti-F IgG and PCA responses. There was a 41% to 44% reduction in 

symptomatic RSV in vaccinees, and a 64% to 75% reduction in RSV LRTD with ≥3 or ≥4 LRTI 

signs / symptoms, respectively. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

milestones. Their development experience focused primarily on viral pathogens. They use the 

technology platform alluded to in that effort. They divide the RSV at-risk population into three 

groups: 

 Older Adults ≥60 years of age 

 Infants, particularly in the first few months of life 

 Children 6 months to 5 years of age 

They have work ongoing that is either in preclinical or early clinical state in pandemic and 

seasonal influenza, combination respiratory (RSV + influenza), and some emerging virus work 

(Ebola and Zika). 

The RSV F vaccine is a BV-Sf9 insect cell-derived recombinant nanoparticle vaccine. It is 

known to produce broadly neutralizing antibodies to three separate epitopes, so it is a purified 

recombinant protein nanoparticle that has at least three epitopes that produce neutralizing 

antibodies. Those are Sites I, II and IV. This vaccine is known to protect animals from 

challenge with wildtype RSV challenge. That has been shown in cotton rat and baboons. 

Multiple Phase 2 trials have been conducted in various populations. 

Beginning with the Phase 2 study in 1600 older adults ≥60 years, this study was conducted 

during the 2014-2015 season. It is a notable trial because it was the first late-stage human trial 

to show vaccine efficacy for any RSV vaccine in any population. It was a randomized 1:1, 

observer blind, placebo controlled trial that utilized 135μg of the RSV F vaccine with no 

adjuvant. The subjects were followed for 1 year for safety, immunogenicity, and efficacy 

endpoints. The study demonstrated a high degree of tolerability and a safety profile that was 

notable for no imbalances between the placebo group and the vaccine group. There were 5­

fold increases in both Palivizumab-competing antibodies (PCA) and Anti-F antibodies measured 

at Day 28 post-vaccination. Importantly, there was a 4.9% placebo attack rate for RSV-acute 

respiratory disease (RSV-ARD) confirmed by RT-PCR. That is comparable to the 5.5% average 

attack rate that Dr. Falsey just presented from the 4-season study in Rochester. Vaccine 

efficacy of 41% was demonstrated against RSV-ARD, which was the primary pre-specified 

endpoint. A post-hoc analysis assessing a more severe endpoint defined as moderate to 

severe lower respiratory tract disease (msLRTD) showed a 64% efficacy against RSV-msLRTD. 

While that was a post-hoc analysis, that was compelling enough in the end of Phase 2 

discussions with the FDA that they decided to make that a primary endpoint for the Phase 3 

trial. They embarked on that Phase 3 trial at the end of November 2015. 

The Phase 3 was called RSV-E-301. This was a large randomized, observer-blind, placebocontrolled trial in 60 US sites with almost 12,000 subjects ≥60 years of age randomized 1:1. 

There were 5921 active arm subjects and 5935 placebo arm subjects. The placebo was 

formulation buffer and the test agent was 135μg RSV F nanoparticle vaccine without adjuvant. 

The primary endpoint for this trial was defined as PCR-confirmed PCR positive msLRTD. For 

mild LRTD, there had to be at least 3 signs or symptoms of LRTD. For severe LRTD, there had 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

to be at least 4 or more signs or symptoms of LRTD. Enrollment was conducted from 

November 9, 2015 through December 12, 2015. Immunogenicity was assessed at 5 time points 

after enrollment. The last patient’s last visit was in June 2016. 

Efficacy was not demonstrated in the Phase 3 trial. There were 28 cases of RSV msLRTD in 

the vaccine arm and 26 cases in the placebo arm, yielding a point estimate of -7.9% with 

confidence intervals ranging from -84 to 37, which is essentially zero efficacy. Comparing that 

to Phase 2 results, there were 5 cases in the RSV-msLRTD arm and 14 in the placebo arm, with 

confidence intervals of 1 to 87. There is about a 4-fold difference in the attack rate in Phase 3 

for this primary end point case definition of 0.44% in the placebo arm versus 1.7% in the Phase 

2 trial. It can be very difficult in Phase 3 trials to demonstrate efficacy when the attack rates are 

this low. The secondary endpoint for efficacy was not met either. There was arguably a modest 

trend toward efficacy with a 12.6% point estimate with confidence intervals of -14 to 33. For 

comparison, there was a sizeable difference in the attack rates in the Phase 2 study. The attack 

rate was under 2% in the Phase 3 trial and almost 5% in the Phase 2 trial, so about a 2.5-fold 

lower attack rate in Phase 3. 

In summary, the safety profile for the Phase 3 trial was consistent with Phase 2 results. There 

were no safety signals, and there were no imbalances between the placebo and vaccine arms. 

The tolerability and reactogenicity profiles were virtually identical with placebo. The RSV-ARD 

and RSV-msLRTD attack rates were markedly lower than expected based on the Phase 2 trial 

and the work that Dr. Falsey conducted in Rochester. The Phase 3 trial failed to show efficacy 

against RSV msLRTD and RSV ARD. There were trends that suggested some positive impact 

on the RSV ARD endpoint and associated healthcare utilization outcomes, but none of these 

was statistically significant. The immunogenicity results observed in the Phase 3 trial are 

broadly consistent with Phase 2 results. This work is still ongoing and has demonstrated robust 

PCA and Anti-F responses and modest increases in microneutralizing antibodies. Analyses in 

search of correlates are ongoing. 

In conclusion, unlike E-201, E-301 failed to show efficacy against RSV ARD or msLRTD, 

although non-significant trends suggest a reduction in RSV ARD and healthcare utilization 

outcomes. However, a few points deserve call-out. The trial was operationally well-conducted 

and randomization was executed correctly. The immunogenicity was exactly what would have 

been expected, demonstrating exactly what was observed in Phase 2 across 3 different assays. 

Investigations to date suggest that there were no product integrity issues. The safety profile of 

the RSV F vaccine remained similar to the placebo and is consistent with E-201. There was no 

clear decrement in the immunogenicity of the vaccine, although work is still being done with 

respect to the immunogenicity data. The RSV attack rate was 2.5- to 4-fold lower than seen in 

E-201 for both msLRTD and ARD, and may have had an impact on the detection of vaccine 

efficacy. This has been an issue with other vaccines. Work that has been done in influenza 

when there was a very low attack rate, made it very difficult to demonstrate vaccine efficacy. 

In terms of moving forward, Novavax is committed to further development of the RSV F vaccine 

construct in older adults. They understand that there are still questions that need to be 

answered with respect to immunogenicity, which is notably more robust in younger adult 

subjects. There are several avenues available for enhanced immunogenicity and / or efficacy 

and Novavax is actively exploring those. The current suite of immunologic endpoints may not 

adequately capture protective responses in the elderly, and additional assay development is 

needed. There also is a need for additional epidemiologic understanding and a more 

sophisticated epidemiologic level of understanding is important, so Novavax appreciates the 

CDC’s work in that respect. The differences observed in the attack rates is one example of 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

where the epidemiology is still something of a conundrum. RSV is only the second annually 

recurring respiratory virus for which late-stage vaccine development has been attempted, and 

RSV appears to evade or modify population immunity in a manner that is different from that of 

influenza. Influenza does this through antigenic drift. It is not exactly clear how RSV does what 

it does, but it seems to modify population immunity in ways that are less than 100% clear. 

Novavax is currently considering dosing or formulation approaches that may overcome 

heterogeneity in background immunity and / or seasonal attack rate differences. 

Novavax’s infant-maternal program is in Phase 3. As far as Dr. Stoddard is aware, this is the 

only RSV vaccine in Phase 3 currently. Three separate Phase 2 trials have been conducted of 

Novavax’s maternal vaccine—2 in women of childbearing age and 1 in pregnant women. 

Multiple animal studies have been conducted, including vaccine challenge studies and 

transplacental antibody transfer studies and a host of other types of studies. An enormous 

amount of work has gone into getting into Phase 3 in the maternal program. 

With respect to the formulation, it is a different vaccine than what is used in older adults. It is 

the same antigenic construct, but with a slightly lower dosage of 120 μg and it is aluminumadjuvanted. It is known from the Phase 2 trials that there is no advantage to giving more than 

one dose. A single dose results in the same response as 2 doses, which is good from a 

pragmatic and programmatic point of view. It is also known that a single aluminum-adjuvanted 

dose provides enhanced neutralizing antibody responses, particularly in young women with the 

lowest pre-immunization titers. That is, those women who have the highest risk of having their 

infants develop RSV bronchiolitis get the most robust response to a single dose of the 

aluminum-adjuvanted vaccine. 

The Phase 2 trial in pregnant women was initiated in September 2014. It involved 50 pregnant 

women at 8 sites in the US during the 2014-2015 RSV season. As mentioned, a 120 μg dose of 

RSV F vaccine + 0.4 mg of aluminum. In the Phase 2 trial, all of the women received the 

vaccine between 33 and 35 weeks of gestation. That window was opened up for the Phase 3 

trials. 

In terms of the safety summary from the Phase 2 trial, the only imbalance of AEs were solicited 

and local. They were predominantly mild to moderate transient injection site pain, which is 

consistent with prior trial in women of child-bearing age. This is expected with any aluminumadjuvanted vaccine in a younger population. There were no SAEs attributed by the 

investigators as causally related. Regarding infant safety, there were no imbalances of AEs 

noted between the placebo and active groups. There were no SAEs attributed as causally 

related to the vaccine. With respect to labor and delivery events, the events monitored were 

determined by Brighton Collaboration guidance. Only a single imbalance was noted, which was 

that the C-section rate was higher in the active group. This was attributed to past obstetrical 

history and not vaccine-related. 

In summary of the Phase 2 RSV F vaccine trial in pregnant women, the vaccine was welltolerated with an acceptable safety profile. The response to the RSV F vaccine in pregnant 

women replicated the immune responses in non-pregnant women from the other two Phase 2 

trials. Maternal antibody seems to peak 14 days post-vaccination. Anti-F, PCA, and 

neutralizing transplacental antibody transfer were all confirmed. There was also noted to be a 

balance of vigorous early antibody response and 100% or higher transplacental transfer in 

women immunized >30 days prior to delivery, which offers flexible timing for antenatal 

immunization. The observed half-life of 41 days for the PCA through the first 60 days postdelivery was also an important finding. This suggests protection of infants for a minimum of 90 

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To determine the efficacy of maternal immunization with the RSV F vaccine against RSV 

lower respiratory tract infection (LRTI) with hypoxemia (SpO2 <95% at sea level or <92% at 

altitudes >1800 meters) through the first 90 days of life in infants of maternal RSV F 

vaccinees as compared to placebo recipients. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

days based on simple first-order decay kinetics, meaning that protective levels might persist 

longer if late elimination kinetics are slower. This will be important in terms of the Phase 3 data. 

The Phase 3 infant-maternal study is now a very large global initiative underway in multiple 

countries throughout the world. A major effort has been made to include many RSV experts 

from around the world, as well as many of the top vaccine clinical trial sites throughout the 

world. This is a randomized, observer-Blind, placebo-controlled, group sequential trial design 

that will be conducted over at least 3 seasons. The trial is currently in season 2. The trial may 

enroll up to 8616 subjects in total globally. In the first year, there were sites in the USA, South 

Africa, Australia, New Zealand, and Chile. Second year additions included Argentina, the UK, 

Spain, Italy, Mexico, and the Philippines. The length of study participation is 9 months for the 

mothers and 1 year for their infants. The window of injection has been extended down to 28 

weeks gestational, making the window of vaccination 28 to 36 weeks. 

A lot of thought and effort were put into defining the primary endpoint for efficacy. Novavax had 

conversations with many top RSV experts from the pediatric community and the pediatric 

infectious disease community and WHO. 

The primary efficacy endpoint is: 

In the event that efficacy is shown through the first 90 days of life, sequential hypothesis 

tests will be carried out to examine efficacy at 120, 150, and 180 days of life. 

The secondary efficacy endpoint is: 

To determine the efficacy of maternal immunization with the RSV F vaccine in reducing the 

incidence of RSV LRTI with severe hypoxemia (SpO2 <92% at sea level or <87% at altitudes 

>1800 meters) or the need for high flow nasal cannula or mechanical ventilatory support; 

RSV LRTI leading to hospitalization; RSV LRTI resulting in death; and all RSV LRTI. 

There is a DSMB that is actively engaged. It is comprised of both pediatric and obstetrical 

experts. They review the study on a regular basis. To date, the formal recommendations made 

by the DSMB have been to continue with this trial with no alternations. There have been no 

apparent safety concerns and no advisements to modify or halt the study to date. 

To summarize, Novavax is committed to pursuing clinical development programs to fully assess 

the safety and efficacy of the RSV F vaccine in populations at highest risk of RSV LRTI. That 

includes RSV LRTI in older adults, as well as RSV LRTI in infants and young children, with 

maternal immunization as the central approach to protecting the youngest infants from 

bronchiolitis and pneumonia. Novavax has a distinguished history of RSV vaccine 

development, with multiple noteworthy contributions to the field and an unwavering commitment 

to addressing a major unmet medical need and a public health priority. 

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Discussion Points 

Given the window of vaccination of pregnant women, Dr. Riley asked whether Novavax is also 

assessing the impact of concomitant immunization with influenza and Tdap vaccines. 

Dr. Stoddard replied that they were not doing this in the Phase 3 trial. It is an important 

question programmatically, and there is some reason to think that based on the older adult trial 

that there may be some immunologic interference between the RSV F vaccine and the influenza 

vaccine. Partly on the basis of that and partly on the basis of needing to run a really clean, 

straightforward, and scientifically pure study, Novavax is not permitting concurrent 

immunization. As important as those vaccines are, in the Phase 3 protocol, they cannot be 

given concurrently with the RSV vaccine because of the confusion it could cause. To be very 

clear, they are not precluding the pregnant women in the Phase 3 trial from getting those 

vaccines, but they are making sure in the protocol that there is some separation in time. 

Dr. Lee said it was great to see this much progress. She requested further information 

regarding the effect modification in the older adult Phase 3 trial in terms of the differences in the 

responsiveness based on whether they had co-administration of influenza vaccine on the same 

day. 

Dr. Stoddard responded that they did observe differences according to concomitant influenza 

and RSV vaccine immunization. For those subjects who received the vaccinations 

concomitantly, there was about a 10% reduction in efficacy observed in the Phase 2 trial. There 

was roughly a 10% reduction in immunogenicity as well. The impact is unidirectional. The 

influenza vaccine negatively impacts the immunogenicity and efficacy of the RSV vaccine, not 

the other way around. 

Given the uncertainty in the attack rates, which seems to be a year-to-year fluctuation, it 

seemed to Dr. Thompson (NVAC) that it would be a good idea to inflate the power calculations 

assuming that the attack rates might be low. It seemed like the sample size was significantly 

too low given the attack rates. 

Dr. Stoddard replied that increasing the sample size in a low attack rate year probably would not 

have made a difference. It is very difficult to demonstrate VE in an exceptionally low attack rate 

year. The point is a good one in terms of better understanding the variation that might occur in 

terms of attack rates with RSV. They may have been naïve in retrospect thinking that 5% was 

about what could be expected year in and year out. Thinking about the data from Fleming in the 

UK that Dr. Falsey discussed, that consistent pattern year in and year out was something that 

investigators had come to believe based on relatively few data points. There needs to be a 

better understanding of what the attack rate is and how much it varies year-to-year. The data 

Dr. Falsey presented are very good in that they captured the fact that there could be broader 

ranges than Novavax anticipated going into its Phase 3 older adult trial. For the maternal trial, 

they do not think this is an issue because they are working in multiple geographies over several 

seasons. 

Dr. Bennett asked if they have hypothesized why the attack rate was so low last year. There 

was variability but also some stability in Dr. Falsey’s data. 

Dr. Stoddard said they wish they knew the answer. It is a great question, but they just do not 

have an answer. There is a lot about RSV epidemiology that is enigmatic and humbles them, 

but they are not giving up. 

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Dr. Messonnier thanked Dr. Stoddard and Novavax for coming before ACIP during this meeting 

to present these data. Everybody likes to present great data, so CDC offered its appreciation 

for Novavax’s willingness to present disappointing data and for the transparency and 

engagement that they have had with ACIP and CDC’s SMEs. 

Dr. Gorman (NIH) commented that understanding that the multiple year study delays approval 

might mitigate Novavax’s risks going forward in the elderly. Regarding the adult study, he 

asked whether Dr. Stoddard was free to discuss which direction they were leaning toward in 

terms of dose or adjuvanting the product. 

Dr. Stoddard replied that they are probably leaning toward both. They are looking at all 

potential options to optimize the immunogenicity of the vaccine in the older adult population. 

Dose and adjuvantation are the two considerations. They will have more to say specifically on 

that in the ensuing weeks. They are still working on exactly what the next study design should 

look like. 

With the wide geographic range and 8000 births, Dr. Gorman (NIH) asked how they will 

operationalize the reality that some of them will be premature and some of them will have lung 

disease. 

Dr. Stoddard responded that this is a complex trial. The premature births will be very difficult to 

analyze. This is going to be a trial that is directed toward analyzing the efficacy in the full-term 

population. 

Paul Offit (Children’s Hospital of Philadelphia) indicated that in the Southern Hemisphere, RSV 

alternates with peaks and troughs. He asked whether Novavax had the capacity in its adult trial 

to follow up those recruits these season, which may be quite a different season than last. 

Dr. Stoddard replied that they are exploring all possibilities, including conducting a Phase 2 

clinically. They are no longer in Phase 3 in the older adults, but are interested in going back to 

Phase 2 for dose ranging and formulation assessments potentially in the Southern Hemisphere. 

That is certainly in the realm of possibilities for them in the coming season. 

Evidence -Based Recommendations Work Group Update 

Wendy Carr, PhD 

ACIP Evidence-Based Recommendations Work Group Lead 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Carr reminded everyone that the purpose of the Evidence-Based Recommendations WG 

(EBRWG) is to provide a forum for discussion of best practices for the evidence-based 

recommendation process for ACIP, including development and use of GRADE evidence tables 

and an evidence to recommendation framework to ensure consistency and enhance 

transparency in the development of ACIP recommendations, with the goal of developing a 

uniform approach to evaluation and use of the evidence base for ACIP recommendations. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report October 19-20, 2016 

In support of this purpose, the aims of the WG defined in the Terms of Reference propose 

additional guidance for the ACIP evidence-based recommendation process, including GRADE 

and subsequent use of an evidence to recommendation framework, specifically for three areas: 

 Improving and harmonizing the development and use of GRADE evidence tables by the 

ACIP WGs 

 Developing criteria to guide the determination of when GRADE evidence tables should be 

prepared in support of a given recommendation 

 Further defining the process of going from the certainty of the evidence base as presented 

by the GRADE tables to recommendations, in particular ensuring that the additional factors 

that contribute to decision-making are considered and communicated. 

Regarding the first aim to harmonize development and use of GRADE tables, several CDC WG 

leads presented their experience using GRADE methodology for past recommendations to the 

WG. Several areas were identified for which additional guidance would be useful. These 

included: 1) applying GRADE methodology to the evaluation of immunogenicity data, including 

further clarifying when evidence should be rated down for indirectness when used as a 

surrogate outcome for efficacy; 2) the acceptability of rating up a body of evidence after 

previously rating it down; 3) the assessment of observational data using GRADE, in particular 

ensuring that the confidence generated by strong observational data is reflected in the ultimate 

evidence rating; and 4) evaluating burden of disease. 

The next steps for moving forward with this goal of harmonizing the development of GRADE 

Tables are to develop draft Frequently Asked Questions (FAQ) documents that provide more 

explicit guidance on how to consistently approach topics that often generate questions during 

the use of GRADE by ACIP WGs. The hope is to draft and gather feedback on these materials 

with a goal of presentation to the ACIP during the June 2017 meeting. 

With respect to the second aim of the WG which centers around providing reference materials, 

to clarify when GRADE should be used to evaluate the evidence for recommendations, the 

intent is to develop a checklist or flowchart to enable WGs to more efficiently determine whether 

GRADE tables should be prepared for a given topic. The intent is to develop draft materials, 

incorporate feedback, and present to ACIP during the June 2017 meeting. 

For the third aim of the WG, to provide additional structure and clarity for the process during 

which factors in addition to the evidence base are considered when formulating 

recommendations, the GRADE WG, a collaboration of methodologists, clinicians, and others 

working to develop, refine, and provide guidance regarding the GRADE evidence-based 

recommendation approach have outlined a process to support movement from evidence to 

decisions. This has been termed Evidence to Decision (EtD) or Evidence to Recommendation 

(EtR) framework. The framework is presented as a table that includes key background 

information, criteria that should be considered, and conclusions. Of note, the certainty of the 

evidence as depicted in GRADE tables is only one consideration in this process and as such is 

only one of the elements of the framework. One advisory group that has adopted the EtR 

framework is the WHO Strategic Advisory Group of Experts on Immunization (SAGE). Members 

of the SAGE Secretariat presented the EtR methodology currently used by SAGE to the 

EBRWG in addition to the discussion of the successes and challenges that have been so far 

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encountered. A recent example of a completed SAGE EtR table can be found at the WHO 

website at this link: http://www.who.int/immunization/policy/position_papers/dengue/en/ 

When queried about potential development of a similar EtR framework for ACIP, feedback from 

members of the EBRWG was positive. Each element of the framework would be customized to 

the needs of ACIP to provide additional structure and clarity in the communication of the 

spectrum of elements considered during recommendation development. The next step is to 

develop a draft ACIP-specific EtR framework, which would be first used to solicit feedback from 

the EBRWG and CDC WG leads for refinement, with a goal of presenting draft materials to 

ACIP during the February 2017 meeting. 

The following is a summation of the proposed timeline for development of additional guidance 

materials: 

 During November / December 2016 and January 2017, the EBRWG meetings will focus on 

specific elements of the EtR framework 

 The draft EtR framework will be presented during the February 2017 ACIP meeting 

 During March, April, and May 2017, the EBRWG will revise the framework and further define 

the elements and will develop and review proposals to address harmonization of GRADE 

usage and when to GRADE evidence 

 The proposals to address key questions will be presented during the June 2017 ACIP 

meeting 

 During the October 2017 ACIP meeting, the final proposals will be presented for an ACIP 

vote on the proposed modifications 

Discussion Points 

Dr. Schaffner (NFID) thought it was wonderful that the EBRWG was addressing the GRADE 

process and adapting it to public health needs. One issue that has frequently arisen in 

discussions as GRADE has been applied is that the indirect effect of vaccines was not 

represented in GRADE, but is often thought to be a huge advantage. He asked whether she 

could address this. 

Dr. Carr acknowledged that indirect effects are not specifically addressed, but pointed out that 

one of the advantages of developing an EtR framework is that it would allow that sort of 

evidence to be incorporated and those considerations to be more clearly presented. 

Dr. Bennett noted that the committee had an opportunity to discuss this at some length the 

previous day and to offer comments at that time. 

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During this session, Dr. Santoli presented an update on the DTaP-containing vaccine Pentacel®, 

BEXSERO®, and adult vaccines. 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Vaccine Supply 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

In December 2015, Sanofi Pasteur announced a manufacturing delay with Pentacel® (DTaPIPV-Hib) vaccine. As a result, Sanofi Pasteur is only able to meet approximately 70% of 

historical Pentacel® vaccine demand. At this time, sufficient supplies of the relevant individually 

administered vaccine antigens are available to address the anticipated gap in the Pentacel® 

supply. Sanofi Pasteur anticipates resolution of this Pentacel® delay sometime during the fourth 

quarter of 2016. 

GSK is currently on back order for both presentations of BEXSERO® (1-pack and 10-pack). 

They anticipate beginning to clear back orders in October. CDC received communication from 

GSK on October 19th that they would be able to resume shipping in the next couple of days. 

However, they anticipate that there will be some shipping delays throughout the fourth quarter of 

2016. GSK does maintain a medical reserve that can be used to fill public or private orders in 

the event of an immediate need, such as an outbreak. The reserve is still available, and GSK is 

currently using this to fill orders as appropriate. 

In terms of adult vaccines, two vial presentations of Merck’s adult vaccines are currently 

unavailable for shipping, the single dose PNEUMOVAX® vial and the 10-pack of single dose 

adult VAQTA® vials. Availability of both of these products is expected to resume the week of 

November 17th. Until that time, Merck has a sufficient supply of the syringe presentation of both 

of these two adult vaccines available to meet the historical demand for both the vial and syringe 

presentations. 

CDC’s Vaccine Supply/Shortage Webpage can be found 

at: www.cdc.gov/vaccines/vac-gen/shortages/default.htm 

Day 2: Public Comment 

No public comments were offered during this session. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Certification 

Upon reviewing the foregoing version of the October 19-20, 2016 ACIP meeting minutes, Dr. 

Nancy Bennett, ACIP Chair, certified that to the best of her knowledge, they are accurate and 

complete. Her original, signed certification is on file with the Management Analysis and 

Services Office (MASO) of CDC. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

ACIP Membership Roster 

September 26, 2016
 

Department of Health and Human Services 

Centers for Disease Control and Prevention
 

Advisory Committee on Immunization Practices
 

July 1, 2016 through June 30, 2017
 

CHAIR 

BENNETT, Nancy, MD, MS 

Professor of Medicine and Public Health Sciences 

Director, Center for Community Health 

Co-director, Clinical and Translational Science Institute 

University of Rochester School of Medicine and Dentistry 

Rochester, NY 

Term: 07/01/2015-06/30/2018 

EXECUTIVE SECRETARY 

COHN, Amanda, MD 

Senior Advisor for Vaccines 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Atlanta, GA 

MEMBERS 

ATMAR, Robert L., MD 

John S. Dunn Clinical Research Professor in Infectious Diseases 

Interim Chief, Section of Infectious Diseases 

Departments of Medicine and Molecular Virology & Microbiology 

Baylor College of Medicine 

Chief, Infectious Diseases Service 

Ben Taub General Hospital, Harris Health System 

Houston, TX 

Term: 7/1/2016 – 6/30/2020 

BELONGIA, Edward, MD 

Director 

Center for Clinical Epidemiology & Population Health 

Marshfield Clinic Research Foundation 

Marshfield, WI 

Term: 07/01/2014-06/30/2018 

EZEANOLUE, Echezona, MD, MPH 

Professor of Pediatrics and Public Health 

Department of Epidemiology and Biostatistics 

Director, Global Health and Implementation Research Initiatives 

University of Nevada 

Las Vegas, NV 

Term: 07/01/2015-06/30/2019 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

HUNTER, Paul, MD 

Associate Professor of Family Medicine and Community Health 

University of Wisconsin School of Medicine and Public Health 

Associate Medical Director 

City of Milwaukee Health Department 

Milwaukee, WI 

Term: 7/1/2016 – 6/30/2020 

KEMPE, Allison, MD, MPH 

Professor of Pediatrics 

Director of Primary Care Fellowship 

University of Colorado School of Medicine 

Director of Research 

Division of General Academic Pediatrics 

Director of Children’s Outcomes Research Program 

The Children’s Hospital of Denver 

Denver, CO 

Term: 07/01/2013 - 06/30/2017 

LEE, Grace M., MD, MPH 

Associate Professor of Population Medicine & Pediatrics 

Director, Center for Healthcare Research in Pediatrics (CHeRP) 

Harvard Pilgrim Health Care Institute & Harvard Medical School 

Associate Medical Director of Infection Control, Boston Children's Hospital 

Boston, MA 

Term: 7/1/2016 – 6/30/2020 

MOORE, Kelly, MD, MPH, 

Director, Tennessee Immunization Program 

Tennessee Department of Health 

Assistant Clinical Professor, Department of Health Policy 

Vanderbilt University School of Medicine 

Nashville, TN 

Term: 07/01/2015-06/30/2019 

PELLEGRINI, Cynthia 

Senior Vice President 

Public Policy and Government Affairs 

March of Dimes 

Washington, DC 

Term: 07/01/2013-06/30/2017 

REINGOLD, Arthur L., MD 

Professor of Epidemiology 

Edward Penhoet Distinguished for Global Health and Infectious Disease 

Associate Dean for Research 

School of Public Health 

University of California 

Berkeley, CA 

Term: 07/01/2013-06/30/2017 

RILEY, Laura E., MD 

180 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Associate Professor, Obstetrics, Gynecology and Reproductive Medicine 

Harvard Medical School 

Maternal Fetal Medicine 

Massachusetts General Hospital 

Boston, MA 

Term: 07/01/2014-06/30/2018 

ROMERO, José R., MD, FAAP 

Professor of Pediatrics 

Horace C. Cabe Endowed Chair in Infectious Diseases 

Director, Pediatric Infectious Diseases Section 

University of Arkansas for Medical Sciences and Arkansas Children's Hospital 

Director, Clinical Trials Research 

Arkansas Children's Hospital Research Institute 

Little Rock, AR 

Term: 07/01/2014-06/30/2018 

STEPHENS, David, MD 

Professor of Medicine, Division of Infectious Diseases 

Chair, Department of Medicine 

Emory University School of Medicine 

Emory University 

Atlanta, GA 

Term: 07/01/2015-06/30/2019 

SZILAGYI, Peter MD, MPH 

Professor of Pediatrics 

Executive Vice-Chair and Vice-Chair for Research 

Department of Pediatrics 

University of California, Los Angeles (UCLA) Los 

Angeles, California 

Term: 7/1/2016 – 6/30-2020 

WALTER, Emmanuel (Chip), Jr., MD, MPH 

Professor of Pediatrics 

Duke University School of Medicine 

Durham, NC 

Term: 07/01/2015-06/30/2019 

EX OFFICIO MEMBERS 

Centers for Medicare and Medicaid Services (CMS) 

HANCE, Mary Beth 

Senior Policy Advisor 

Division of Quality, Evaluations and Health Outcomes 

Children and Adults Health Programs Group 

Center for Medicaid, CHIP and Survey & Certification 

Centers for Medicare and Medicaid Services 

Baltimore, MD 

181 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

Department of Defense (DoD) 

Department of Defense (DoD) DEUSSING, ERIC, MD, MPH 

Commander, Medical Corps, United States Navy 

Department of Defense Liaison 

Centers for Disease Control and Prevention 

Atlanta, GA 

Department of Veterans Affairs (DVA) 

KIM, Jane A., MD, MPH 

Deputy Chief Consultant for Preventive Medicine 

Office of Patient Care Services 

National Center for Health Promotion and Disease Prevention 

Durham, North Carolina 

Food and Drug Administration (FDA) 

SUN, Wellington, MD 

Director, Division of Vaccines and Related Product Applications 

Office of Vaccines Research and Review 

Food and Drug Administration 

Rockville, MD 

Health Resources and Services Administration (HRSA) 

NAIR, Narayan, MD 

CAPT, USPHS 

Acting Division Director/Chief Medical Officer 

Division of Injury Compensation Programs 

Healthcare Systems Bureau 

Rockville, MD 

Indian Health Service (IHS) 

GROOM, Amy, MPH 

Immunization Program Manager 

Indian Health Service 

Albuquerque, NM 

National Vaccine Program Office (NVPO) 

GELLIN, Bruce, MD, MPH 

Director 

National Vaccine Program Office 

Department of HHS, Public Health and Science 

Washington, DC 

National Institutes of Health (NIH) 

GORMAN, Richard L., MD 

Associate Director for Clinical Research 

Division of Microbiology and Infectious Diseases/NIAID 

National Institute of Health 

Bethesda, MD 

182 

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American College of Nurse Midwives (ACNM) (alternate) 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

LIAISON REPRESENTATIVES 

American Academy of Family Physicians (AAFP) 

SAVOY, Margot, MD, MPH 

Medical Director, Department of Family & Community Medicine 

Christiana Care Health System 

Wilmington, DE 

American Academy of Pediatrics (AAP) 

BYINGTON, Carrie L., MD 

Chair, AAP Committee on Infectious Diseases 

H.A. and Edna Benning Presidential Professor of Pediatrics 

Associate Vice President for Faculty and Academic Affairs 

University of Utah Health Sciences Center 

Salt Lake City, UT 

American Academy of Pediatrics (AAP) 

Red Book Editor 

KIMBERLIN, David, MD 

Professor of Pediatrics 

Division of Pediatric Infectious Diseases 

The University of Alabama at Birmingham School of Medicine 

Birmingham, AL 

American Academy of Physician Assistants (AAPA)

LÉGER, Marie-Michèle, MPH, PA-C 

Senior Director, Clinical and Health Affairs 

American Academy of Physician Assistants 

Alexandria, VA 

American College Health Association (ACHA) 

EVEN, Susan, MD 

Executive Director 

Student Health Center 

University of Missouri 

Columbia, MO 

American College of Nurse Midwives (ACNM) 

HAYES, Carol E., CNM, MN, MPH 

Atlanta Perinatal Associates 

Atlanta, GA 

MEHARRY, Pamela M., PHD, CNM 

Midwifery Educator, Human Resources for Health 

In partnership with University of Rwanda and University of Illinois, Chicago 

183 

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American College of Physicians (ACP) (alternate) 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

American College of Obstetricians and Gynecologists (ACOG) 

AULT, Kevin A., MD, FACOG 

Professor and Division Director 

Department of Obstetrics and Gynecology 

University of Kansas Medical Center 

Kansas City, KS 

American College of Physicians (ACP) 

FRYHOFER, Sandra Adamson., MD, MACP 

Adjunct Associate Professor of Medicine 

Emory University School of Medicine 

Atlanta, GA 

POLAND, Gregory A., MD 

Mary Lowell Professor of Medicine and Infectious Diseases 

Mayo Clinic 

Rochester, MN 

American Geriatrics Society (AGS) 

SCHMADER, Kenneth, MD 

Professor of Medicine-Geriatrics 

Geriatrics Division Chief 

Duke University and Durham VA Medical Centers 

Durham, NC 

America’s Health Insurance Plans (AHIP) 

NETOSKIE, Mark J., MD, MBA 

Market Medical Executive, CIGNA 

Houston, TX 

American Medical Association (AMA) 

FRYHOFER, Sandra Adamson., MD 

Adjunct Associate Professor of Medicine 

Emory University School of Medicine 

Atlanta, GA 

American Nurses Association (ANA) 

RITTLE, Charles (Chad), DNP, MPH, RN 

Assistant Professor, Nursing Faculty 

Chatham University, School of Health Sciences 

Pittsburgh, PA 

American Osteopathic Association (AOA) 

GROGG, Stanley E., DO 

Associate Dean/Professor of Pediatrics 

Oklahoma State University-Center for Health Sciences 

Tulsa, OK 

184 

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Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

American Pharmacists Association (APhA) 

FOSTER, Stephan L., PharmD 

Professor and Vice Chair, Department of Clinical Pharmacy 

University of Tennessee Health Sciences Center, College of Pharmacy 

Memphis, TN 

Association of Immunization Managers (AIM) 

FINLEY, Christine, RN, MPH 

Immunization Program Manager 

Vermont Department of Health 

Burlington, VT 

Association for Prevention Teaching and Research (APTR) 

McKINNEY, W. Paul, MD 

Professor and Associate Dean 

University of Louisville School of Public Health and Information Sciences 

Louisville, KY 

Association of State and Territorial Health Officials (ASTHO) 

DWELLE, Terry L, MD, MPHTM 

State Health Officer 

North Dakota Department of Health 

Bismarck, ND 

Biotechnology Industry Organization (BIO) 

ARTHUR, Phyllis A., MBA 

Senior Director, Vaccines, Immunotherapeutics and Diagnostics Policy 

Washington, DC 

Council of State and Territorial Epidemiologists (CSTE) 

HAHN, Christine, MD 

State Epidemiologist 

Office of Epidemiology, Food Protection and Immunization 

Idaho Department of Health and Welfare 

Boise, ID 

Canadian National Advisory Committee on Immunization (NACI) 

GEMMILL, Ian MacDonald, MD 

Medical Officer of Health 

Kingston, Frontenac and Lennox & Addington Public Health 

Kingston, Ontario, Canada 

Infectious Diseases Society of America (IDSA) 

NEUZIL, Kathleen M., MD, MPH 

Professor of Medicine 

Director, Center for Vaccine Development 

University of Maryland School of Medicine 

Baltimore, MD 

185 

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Infectious Diseases Society of America (IDSA) (alternate) 

 

National Association of County and City Health Officials (NACCHO) (alternate) 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

BAKER, Carol J., MD 

Professor of Pediatrics 

Molecular Virology and Microbiology 

Baylor College of Medicine 

Houston, TX 

National Association of County and City Health Officials (NACCHO) 

ZAHN, Matthew, MD 

Medical Director, Epidemiology 

Orange County Health Care Agency 

Santa Ana, CA 

DUCHIN, Jeffrey, MD 

Health Officer and Chief, Communicable Disease Epidemiology and Immunization Section 

Public Health - Seattle and King County 

Professor in Medicine 

Division of Allergy and Infectious Diseases 

University of Washington School of Medicine and School of Public Health 

Seattle, WA 

National Association of Pediatric Nurse Practitioners (NAPNAP) 

STINCHFIELD, Patricia A., RN, MS, CPNP 

Director 

Infectious Disease/Immunology/Infection Control 

Children's Hospitals and Clinics of Minnesota 

St. Paul, MN 

National Foundation for Infectious Diseases (NFID) 

SCHAFFNER, William, MD 

Chairman, Department of Preventive Medicine 

Vanderbilt University School of Medicine 

Nashville, TN 

National Immunization Council and Child Health Program, Mexico

VILLASEÑOR RUIZ, Ignacio, MD 

Directora del Programa de Atencion da la Salud de la Infancia y la Adolescencia / Director 

General, Child and Adolescent Health 

Centro Nacional Para la Salud de la Infancia Y La Adolescencia / National Center for Child and 

Adolescent Health 

Ministry of Health / Secretaría de Salud 

Mexico 

National Medical Association (NMA) 

WHITLEY-WILLIAMS, Patricia, MD 

Professor and Chair 

University of Medicine and Dentistry of New Jersey 

Robert Wood Johnson Medical School 

New Brunswick, NJ 

186 

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Pediatric Infectious Diseases Society (PIDS) 

Pediatric Infectious Diseases Society (PIDS) (alternate) 

Advisory Committee on Immunization Practices (ACIP) Summary Report October 19-20, 2016 

National Vaccine Advisory Committee (NVAC) 

THOMPSON, Kimberly, ScD 

Chair, NVAC 

Professor of Preventive Medicine and Global Health 

University of Central Florida, College of Medicine Orlando, FL 

O’LEARY, Sean, MD, MPH 

Associate Professor of Pediatrics 

Pediatric Infectious Diseases 

General Academic Pediatrics 

Children’s Hospital Colorado 

University of Colorado School of Medicine 

SAWYER, Mark H, MD 

Professor of Clinical Pediatrics 

University of California, San Diego School of Medicine 

San Diego, CA 

Pharmaceutical Research and Manufacturers of America (PhRMA) 

JOHNSON, David R, MD, MPH 

Associate Vice President, Global Medical Affairs, Sanofi Pasteur 

Swiftwater, PA 

Society for Adolescent Health and Medicine (SAHM) 

MIDDLEMAN, Amy B., MD, MSEd, MPH 

Professor of Pediatrics 

Chief, Section of Adolescent Medicine 

University of Oklahoma Health Sciences Center 

Oklahoma City, OK 

Society for Healthcare Epidemiology of America (SHEA) 

WEBER, David, MD, MPH 

Professor of Medicine, Pediatrics, and Epidemiology 

University of North Carolina Schools of Medicine and Public Health 

Medical Director, Hospital Epidemiology and Occupational Health, UNC Health Care 

University of North Carolina 

Chapel Hill, NC 

187 

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