DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION 

NATIONAL IMMUNIZATION PROGRAM 

Advisory Committee on Immunization Practices 

June 29-30, 2006 

Atlanta, Georgia

Record of the Proceedings 

This document has been archived for historical purposes. (7/1/2006)
TABLE OF CONTENTS

Page

Attachment 1: List of Participants ...........................................................................................................A1.1 

Attachment 2: Acronyms Used In This Report........................................................................................A2.1 

Minutes of the Meeting.................................................................................................................................. 1 

June 29, 2006

 Opening Session .................................................................................................................................... 1 

 HUMAN PAPILLOMAVIRUS VACCINE................................................................................................. 2

 Overview .......................................................................................................................................... 2 

 GARDASIL®

 Efficacy and Safety Data............................................................................................. 3 

 GARDASIL®

 Risk Management Plan............................................................................................... 7 

 GARDASIL®

 Post-Marketing Safety Surveillance............................................................................ 9 

 Potential Cost-Effectiveness of HPV Vaccination in the United States ......................................... 10 

 Public Comment Period ................................................................................................................. 12 

 Proposed Recommendations for the Quadrivalent HPV Vaccine.................................................. 16 

 ACIP Vote on the HPV Vaccine..................................................................................................... 18 

 Proposed VFC Resolution ............................................................................................................. 21 

 ACIP Vote on the Proposed VFC Resolution ................................................................................ 21 

 VARICELLA VACCINE......................................................................................................................... 22 

 Update on Varicella Epidemiology ................................................................................................. 22 

 Immune Responses to One and Two Doses of Varicella Vaccine ................................................ 24 

 Projected Benefits and Costs of a Second Dose of Varicella Vaccine.......................................... 26 

 State Health Department Perspective on Varicella Outbreak Response ...................................... 27 

 Consideration of a Universal Two-Dose Recommendation for Varicella Immunization ................ 28 

 ACIP Vote on the Varicella Vaccination Policy .............................................................................. 33

 Proposed VFC Resolution ............................................................................................................. 35 

 ACIP Vote on the Proposed VFC Resolution ................................................................................ 35 

 INFLUENZA VACCINE......................................................................................................................... 36 

 Next Steps in Decreasing Influenza-Associated 

 Morbidity and Mortality Through Annual Vaccination .................................................................... 36 

 One Versus Two Doses of Trivalent Inactivated Influenza Vaccine in 

 Influenza Vaccine-Naïve Children.................................................................................................. 39 

 Options for Children Who Were Not Fully Vaccinated Initially....................................................... 40 

 ACIP Vote on Options for Children Who Were Not Fully Vaccinated Initially................................ 41 

 Options for Tiered Use of TIV ........................................................................................................ 42 

 ACIP Vote on Options for Tiered Use of TIV ................................................................................. 44

 ISO Update........................................................................................................................................... 45 

 Public Comment Period........................................................................................................................ 47 

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TABLE OF CONTENTS

Page

June 30, 2006

 Update on Menactra®

 Supply and Prioritization ................................................................................... 48 

 Tdap VACCINE IN PREGNANT WOMEN ........................................................................................... 49 

 Pertussis Workgroup Report.......................................................................................................... 50 

 Considerations for Tdap in Pregnant Women................................................................................ 50 

 Draft Recommendations for Tdap in Pregnant Women................................................................. 53 

 ACIP Vote on the Draft Recommendations for Tdap in Pregnant Women.................................... 55 

 Adult Immunization Schedule for October 2006-September 2007....................................................... 57 

 Update on Pneumococcal Vaccines..................................................................................................... 57 

 HERPES ZOSTER (SHINGLES) VACCINE ........................................................................................ 60 

 Evaluation of the Vaccine Cost-Effectiveness ............................................................................... 60

 Projected Cost Effectiveness of Vaccinating the Elderly to Prevent Shingles............................... 63 

 Overview of the ZOSTAVAX®

 Storage, Handling and RMP.......................................................... 66 

 Considerations for Shingles Vaccine Recommendations in the United States ............................. 67 

 Childhood/Adolescent Immunization Schedule for 2007...................................................................... 70 

 Update on the Multi-State Mumps Outbreak in the United States ....................................................... 73 

 Update on the Rotavirus Vaccine......................................................................................................... 76 

Ex- Officio Reports................................................................................................................................ 77 

 Public Comment Period........................................................................................................................ 78 

 Closing Session.................................................................................................................................... 79 

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Page A1.1 

ATTACHMENT 1 

List of Participants

ACIP Members

Dr. Jon Abramson, Chair 

Dr. Ban Mishu Allos 

Mr. Robert Beck 

Dr. Judith Campbell 

Dr. Reginald Finger 

Dr. Janet Gilsdorf 

Dr. Harry Hull 

Dr. Tracy Lieu 

Dr. Edgar Marcuse 

Dr. Julia Morita 

Dr. Dale Morse 

Dr. Gregory Poland 

Ms. Patricia Stinchfield 

Dr. John Treanor 

Dr. Robin Womeodu 

Designated Federal Official

Dr. Larry Pickering 

ACIP Executive Secretary 

Liaison and Ex- Officio Representatives

Dr. Carol Baker 

American Academy of Pediatrics 

Dr. Doug Campos-Outcalt 

American Academy of Family Physicians 

Dr. James Cheek 

Indian Health Service 

Dr. George Curlin 

National Institutes of Health 

Dr. Geoffrey Evans 

Health Resources and Services Administration 

Dr. Stephen Ford 

Department of Defense 

Dr. Stephan Foster 

American Pharmacists Association 

Dr. Gary Freed 

National Vaccine Advisory Committee 

Dr. Stanley Gall 

American College of Obstetricians and 

Gynecologists 

Dr. Bruce Gellin 

National Vaccine Program Office 

Dr. Andrea Gelzer 

America’s Health Insurance Plans 

Dr. Karen Goldenthal 

Food and Drug Administration 

Dr. Samuel Katz 

Infectious Diseases Society of America 

Dr. Clement Lewin 

Biotechnology Industry Organization 

Dr. Cody Meissner 

American Academy of Pediatrics 

Dr. Amy Middleman 

Society for Adolescent Medicine 

Ms. Linda Murphy 

Centers for Medicare and Medicaid Services 

Dr. Monica Naus 

Canadian National Advisory Committee on 

Immunization

Dr. Kathleen Neuzil 

American College of Physicians 

Dr. Kristin Nichol [via conference call] 

Department of Veterans Affairs 

Dr. Peter Paradiso 

Pharmaceutical Research and Manufacturers of 

America 

Dr. Keith Powell 

American Academy of Pediatrics 

Dr. Romeo Rodriquez 

National Immunization Council and Child Health 

Program, Mexico 

Dr. William Schaffner 

National Foundation for Infectious Diseases 

This document has been archived for historical purposes. (7/1/2006)
Dr. Litjen Tan 

American Medical Association 

Dr. Jonathan Temte 

American Academy of Family Physicians 

Dr. James Turner 

American College Health Association 

Dr. Patricia Whitley-Williams 

National Medical Association 

CDC Representatives

Dr. Larry Anderson 

Dr. William Atkinson 

Dr. James Baggs 

Ms. Michelle Basket 

Dr. Vicki Benard 

Dr. Stuart Berman 

Dr. Achal Bhatt 

Dr. Carolyn Bridges 

Dr. Karen Broder 

Dr. Angela Calugar 

Dr. Sandra Chaves 

Dr. Harrell Chesson 

Dr. David Coole 

Ms. Margaret Cortese 

Mr. Cary Cox 

Ms. Katie Crocker 

Ms. Deblina Datta 

Ms. Jill Davila 

Dr. Robert Davis 

Dr. Gustavo Dayan 

Dr. Frank DeStefano 

Dr. John Douglas 

Ms. Eileen Dunne 

Dr. Gary Euler 

Dr. Susan Farrall 

Dr. Daniel Fishbein 

Ms. Allison Friedman 

Ms. MariBeth Gagnon 

Ms. Sandra Gambescia 

Ms. Demetria Gardner 

Dr. Paul Gargiullo 

Dr. Roger Glass 

Dr. Sami Gottlieb 

Ms. Anna Green 

Dr. Sophia Greer 

Dr. Dalya Guris 

Ms. Jennifer Hamborsky 

Dr. Rafael Harpaz 

Ms. Rita Helfand 

Ms. Stacey Hoffman 

Dr. John Iskander 

Dr. Kashif Iqbal 

Dr. Robert Johnson 

Dr. Hannah Jordan 

Dr. Pat Joyce 

Dr. Katrina Kretsinger 

Dr. Andrew Kroger 

Dr. Derrick Lake 

Dr. Hershel Lawson 

Dr. Jessica Leung 

Dr. Susan Lett 

Ms. Nicole Liddon 

Dr. Suchita Lorick 

Dr. Susan Manning 

Dr. Mona Marin 

Dr. Lauri Markowitz 

Ms. Stacey Martin 

Dr. Eric Mast 

Dr. Christina Mijalski 

Ms. Elaine Miller 

Dr. Matthew Moore 

Dr. Gina Mootrey 

Dr. John Moran 

Dr. Julianne Morita 

Dr. Trudy Murphy 

Dr. Siobhan O’Connor 

Dr. Ismael Ortega-Sanchez 

Dr. Umesh Parashar 

Dr. Roopal Patel 

Ms. Bette Pollard 

Dr. Pamela Protzel-Berman 

Dr. Aaron Rak 

Dr. Stephanie Renna 

Dr. Meredith Reynolds 

Dr. Donna Rickert 

Dr. Lance Rodewald 

Dr. Paul Rota 

Ms. Sandy Roush 

Ms. Teresa Rutledge 

Ms. Tammy Santibanez 

Dr. Jeanne Santoli 

Ms. Mona Saraiya 

Dr. Scott Schmid 

Dr. Anne Schuchat 

Dr. Jane Seward 

Dr. Tom Shimabukuro 

Dr. James Singleton 

Ms. Barbara Slade 

Dr. Jeanne Smith 

Dr. Nicole Smith 

Dr. Pamela Srivastava 

Dr. William Thompson 

Dr. Tejpratap Tiwari 

Ms. Maria Lucia Tondella 

Dr. Charles Vitek 

Dr. Gregory Wallace 

Dr. Margaret Watson 

Dr. Donna Weaver 

Dr. Melinda Wharton 

This document has been archived for historical purposes. (7/1/2006)
Dr. Marc-Alain Widdowson 

Dr. Skip Wolfe 

Ms. Kimberly Workowski 

Dr. Fujie Xu 

Dr. Eileen Yee 

Dr. Fangjun Zhou 

Guest Presenters, Press and 

Members of the Public

Mr. Savant Ahmed 

HSBC Securities 

Dr. Vincent Ahonkhai 

GlaxoSmithKline Pharmaceuticals 

Dr. Jennifer Allen 

Merck & Co., Inc. 

Mr. Stephen Allred 

Get A Flu Shot.com 

Mr. Gregory Allsberry 

National Autism Recovery Foundation 

Ms. Karla Allsberry 

National Autism Recovery Foundation 

Dr. Paula Annunziato 

Merck & Co., Inc. 

Ms. Deborah Arrindell 

American Social Health Association 

Mr. Allen Arthur 

Slate.com 

Dr. Phyllis Arthur 

Merck & Co., Inc. 

Dr. Kevin Ault 

Emory University School of Medicine 

Dr. Howard Backer 

California Department of Health Services 

Dr. Lynn Bahta 

Minnesota Department of Health 

Mr. Scott Bales 

Autism Society of America-Georgia Chapter 

Dr. Allyn Bandell 

MedImmune, Inc. 

Dr. Dennis Barnes 

GlaxoSmithKline Pharmaceuticals 

Dr. Eliav Barr 

Merck Research Laboratories 

Dr. Jay Bauman 

MedImmune, Inc. 

Mr. David Beauvais 

Generation Rescue 

Ms. Karen Beauvais 

Generation Rescue 

Mr. Evan Bedil 

Marathon Asset Management 

Dr. Graeme Bell 

Merck & Co., Inc. 

Dr. Soubeyrand Benoit 

sanofi pasteur 

Dr. Joan Benson 

Merck & Co., Inc. 

Dr. Karyn Berry 

District of Columbia Department of Health 

Ms. Kerry Bloch 

Moms Against Mercury 

Mr. Robert Bloch 

A-CHAMP 

Dr. Joseph Bocchini 

American Academy of Pediatrics 

Ms. Laura Bono 

National Autism Association 

Mr. Scott Bono 

National Autism Association 

Ms. Donna Bopp 

Northeast Health District 

Mr. Andrew Bowser 

AB Writing and Editing, Inc. 

Dr. Kimberly Bradley 

Merck Vaccine Division 

Dr. Otis Brawley 

Winship Cancer Institute 

Ms. Nicole Brier 

sanofi pasteur 

This document has been archived for historical purposes. (7/1/2006)
Dr. Dennis Brooks 

Merck & Co., Inc. 

Ms. Kristin Brown 

SAIC 

Dr. Philip Brunell 

National Institutes of Health 

Professor Margaret Burgess 

National Centre for Immunisation Research 

Ms. Barbie Bushey 

Northeast Health District 

Ms. Jennifer Byrnes 

Surveillance Data, Inc. 

Ms. Amy Carson 

Public 

Dr. Michael Channey 

American Academy of Pediatrics 

Dr. Deborah Charsha-May 

MedImmune, Inc. 

Dr. Peter Chattin 

GlaxoSmithKline Pharmaceuticals 

Dr. Veronica Chollette 

National Cancer Institute 

Dr. Liana Clark 

Merck & Co., Inc. 

Ms. Lujene Clark 

Public 

Ms. Nicole Clarke 

Capital Royalty, LP 

Mr. Richard Clover 

University of Louisville 

Dr. Kathy Coelingh 

MedImmune Vaccines 

Dr. Chris Colwell 

Biotechnology Industry Organization 

Dr. John Cook 

Merck Research Laboratories 

Ms. Lenore Cooney 

Cooney/Waters Group 

Ms. Jennifer Corbett 

Dow Jones & Co. 

Mr. John Crouch 

ASD Solutions 

Mr. Roberto Cuca 

JP Morgan 

Dr. Joseph DaBronzo 

sanofi pasteur 

Mr. Donald Dalrymple 

Dalrymple & Associates, LLC 

Dr. Adrian Dana 

Merck & Co, Inc. 

Mr. Mike D’Anthony 

Sound On-Site, Inc. 

Dr. Erik Dasbach 

Merck Research Laboratories 

Ms. Ana Dayton 

Constella Group 

Dr. Carolyn Deal 

National Institute of Allergy and Infectious 

Diseases 

Dr. Roberto Debbag 

sanofi pasteur and National Children’s Hospital 

Ms. Anna DeBlois 

Association of State and Territorial Health 

Officials 

Dr. Michael Decker 

sanofi pasteur and Vanderbilt University 

Dr. Shelly Deeks 

Public Health Agency of Canada 

Dr. Kenneth Dennison 

Wyeth Pharmaceuticals 

Ms. Sarah Despres 

House Government Reform Committee 

Dr. Richard Dinovitz 

Wyeth Vaccines 

Dr. Jag Dosanjh 

GlaxoSmithKline Pharmaceuticals 

This document has been archived for historical purposes. (7/1/2006)
Dr. Kelley Dougherty 

Merck & Co., Inc. 

Mr. Jeffrey Duchin 

National Association of City and County Health 

Officials 

Dr. Colleen Duffy 

Merck Vaccine Division 

Dr. Laurel Edelman 

Surveillance Data, Inc. 

Dr. Kristen Ehresmann 

Minnesota Department of Health 

Dr. Elamin Elbasha 

Merck & Co., Inc. 

Mr. Jim Evans 

Sound On-Site, Inc. 

Dr. Judith Falloon 

National Institute of Allergy and Infectious 

Diseases 

Dr. Christine Fanelle 

Merck & Co., Inc. 

Dr. Mark Feinberg 

Merck Vaccine Division 

Dr. Stephen Ford 

Military Vaccine Agency 

Dr. Serene Forte 

MedImmune, Inc. 

Ms. Wendy Fournier 

National Autism Association 

Ms. Susan Fox 

Medical Knowledge Group 

Dr. Vincent Frascatore 

Merck & Co., Inc. 

Ms. Tammy Freeman 

Kennesaw State University 

Dr. Marisa Frost 

Children’s Healthcare of Atlanta 

Dr. Sylvina Frutos 

GlaxoSmithKline Pharmaceuticals 

Dr. Sandra Fryhofer 

American College of Physicians 

Ms. Diane Gaffoglio 

Nancy Lee & Associates 

Dr. Susan Garfield 

Digene Corporation 

Dr. Matthew Garrett 

Wyeth Vaccines 

Ms. Diana Gaskins 

Georgia Immunization Program 

Mr. Jeffrey George 

TDG, Inc. 

Dr. Anne Gershon 

Columbia University 

Ms. Ruth Gilmore 

Georgia Immunization Program 

Dr. Mark Gorman 

National Coalition for Cancer Survivorship 

Ms. Elizabeth Goss 

Ropes & Gray 

Dr. Michelle Goveia 

Merck & Co., Inc. 

Mr. Michael Green 

International Recurrent Respiratory 

Papillomatosis Information, Support and 

Advocacy Center 

Dr. Amy Groom 

Indian Health Service 

Dr. Jill Hackell 

Wyeth Vaccines 

Dr. Neal Halsey 

Johns Hopkins University 

Dr. Danielle Halstrom 

GlaxoSmithKline Pharmaceuticals 

Dr. Sandra Hammer 

California Department of Health Services 

Ms. Michelle Hannah 

Celebrate Life Foundation 

This document has been archived for historical purposes. (7/1/2006)
Dr. Claire Hannan 

Association of Immunization Managers 

Ms. Dionne Hansey 

Northeast Health District 

Ms. Alexandra Hauber 

Bear Sterns 

Dr. Richard Haupt 

Merck & Co., Inc. 

Ms. Patti Hawkins 

Generation Rescue 

Dr. Vincent Haynes 

MedImmune, Inc. 

Dr. Dominic Hein 

GlaxoSmithKline Biologicals 

Dr. Pierre Jules Hein 

GlaxoSmithKline Biologicals 

Mr. Curtis Hermann 

SciMed 

Dr. Teresa Hesley 

Merck & Co., Inc. 

Mr. Daniel Hopfensperger 

Wisconsin Immunization Program and 

Association of Immunization Managers 

Dr. Philip Hosbach 

sanofi pasteur 

Mr. Mike Huckman 

CNBC 

Dr. Gina Hunt 

Merck & Co., Inc. 

Dr. Jennifer Huntington 

Emergent BioSolutions 

Dr. Shirley Jankelevich 

South Carolina Department of Health 

Dr. David Jenkins 

GlaxoSmithKline Biologicals 

Ms. Alice Johnson 

St. Louis City Department of Health 

Dr. David Johnson 

sanofi pasteur 

Dr. Brian Katzowitz 

Children’s Healthcare of Atlanta 

Cmdr. Stephen Kay 

Generation Rescue 

Ms. Sara Keeley 

Kennesaw State University 

Mr. Samuel Kim 

Prudential Equity Group, LLC 

Dr. David Kimberlin 

American Academy of Pediatrics Committee on 

Infectious Diseases 

Dr. Walter Kimble 

Merck & Co., Inc. 

Dr. Sarah Kobrin 

National Cancer Institute 

Ms. Emma Kofa 

National Association of County and City Health 

Officials 

Dr. Jeffrey Koplan 

Emory University 

Mr. Robert Krakow 

Advocates for Children’s Health Affected by 

Mercury Poisoning 

Dr. Charlotte Kroft 

GlaxoSmithKline Pharmaceuticals 

Dr. Denise Kruzikas 

GlaxoSmithKline Pharmaceuticals 

Dr. Barbara Kuter 

Merck & Co., Inc. 

Dr. Jamie Lacey 

MedImmune, Inc. 

Senator Gloria Lawlah (Maryland) 

Women in Government 

Dr. Sarah Landry 

GlaxoSmithKline Pharmaceuticals 

Ms. Laura Larson 

Tanner Health System 

This document has been archived for historical purposes. (7/1/2006)
Dr. Philip LaRussa 

Columbia University 

Dr. Len Lavenda 

sanofi pasteur 

Dr. Francois Lebel 

MedImmune, Inc. 

Ms. Kay Lee 

Generation Rescue 

Ms. Marie-Michele Leger 

American Academy of Physician Assistants 

Dr. Michelle Lesher 

Merck & Co., Inc. 

Dr. Myron Levin 

University of Colorado School of Medicine 

Dr. Edward Lewin 

MedImmune, Inc. 

Dr. Julie Liaw 

Chicago Department of Public Health 

Dr. Kai-Li Liaw 

Merck Research Laboratories 

Dr. Patrick Liedtka 

Merck & Co., Inc. 

Dr. Christopher Loder 

Merck & Co., Inc. 

Dr. Christine Loeb 

GlaxoSmithKline Pharmaceuticals 

Dr. Peter Loesher 

Merck & Co., Inc. 

Dr. Beverly Lybrand 

Merck & Co., Inc. 

Dr. Peter MacDonald 

MedImmune, Inc. 

Dr. Andrew MacKnight 

GlaxoSmithKline Pharmaceuticals 

Dr. Leonardo Maggi 

Universidad de Chile and sanofi pasteur 

Dr. Doris Makari 

MedImmune, Inc. 

Ms. Shibani Malhotra 

Morgan Stanley 

Ms. Susan Malone 

Coastal Health District 9-1 

Ms. Bobbie Manning 

Advocates for Children’s Health Affected by 

Mercury Poisoning 

Mr. Michael Manning 

Advocates for Children’s Health Affected by 

Mercury Poisoning 

Dr. Patrick Maroney 

sanofi pasteur Vaccines 

Dr. Cesar Mascarei as de los Santos 

sanofi pasteur 

Dr. Dean Mason 

Wyeth Vaccines 

Ms. Kay Mason 

Generation Rescue 

Dr. Marie Mazur 

CSL Biotherapies 

Dr. Margie McGlynn 

Merck & Co., Inc. 

Dr. Yvonne McHugh 

Novartis Vaccines 

Dr. Peter McIntyre 

National Centre for Immunisation Research 

Dr. Yves Megard 

sanofi pasteur 

Ms. Lynne Mercedes 

Georgia Division of Public Health 

Ms. Gwen Miller 

Massvax Travel Clinic, LLC 

Mr. James Moody 

Sensible Action For Ending Mercury-Induced 

Neurological Disorders (SafeMinds) 

Ms. Kelly Moore 

Tennessee Department of Health 

This document has been archived for historical purposes. (7/1/2006)
Dr. Charlotte Moser 

The Children’s Hospital of Philadelphia Vaccine 

Education Center 

Ms. Linda Moyer 

Immunization Action Coalition 

Mr. Richard Moyer 

Public 

Dr. Martin Myers 

National Network for Immunization Information 

Dr. Thomas Netzer 

Merck & Co., Inc. 

Dr. Karen Nielsen 

GlaxoSmithKline Pharmaceuticals 

Dr. Timothy Obara 

GlaxoSmithKline Pharmaceuticals 

Dr. Paul Offit 

The Children’s Hospital of Philadelphia 

Dr. Robert Oliver 

Wyeth Pharmaceuticals 

Dr. Niki Oquist 

MedImmune, Inc. 

Dr. Walter Orenstein 

Emory University 

Dr. Esther Paek 

Merck & Co., Inc. 

Dr. James Pellissier 

Merck Research Laboratories 

Dr. Georges Peter 

Brown Medical School 

Ms. Diane Peterson 

Immunization Action Coalition 

Dr. Stanley Plotkin 

Emeritus Professor of Virology 

Dr. Geoffrey Porges 

Sanford C. Bernstein & Co., LLC 

Dr. Jane Quinn 

GlaxoSmithKline Pharmaceuticals 

Dr. Pamela Rasmussen 

Digene Corporation 

Dr. Mobeen Rathore 

University of Florida 

Ms. Kate Rawson 

The RPM Report 

Ms. Lyn Redwood 

Sensible Action For Ending Mercury-Induced 

Neurological Disorders (SafeMinds) 

Dr. Stella Reed 

Merck & Co., Inc. 

Dr. Margaret Rennels 

GlaxoSmithKline Pharmaceuticals 

Dr. Debbag Roberto 

sanofi pasteur 

Dr. Robin Robinett 

CSL Biotherapies 

Dr. Loleta Robinson 

MedImmune 

Dr. Francisco Rosales 

Mexico Bioprevencion Inmunization Center 

Dr. Paula Rose 

GlaxoSmithKline Pharmaceuticals 

Dr. Denise Ross 

AmeriChoice 

Dr. Beth Rowe-West 

North Carolina Immunization Branch 

Ms. Judith Rusk 

SLACK, Inc. 

Dr. Alfred Saah 

Merck & Co., Inc. 

Dr. Thomas Saari 

American Academy of Pediatrics Task Force on 

Immunization

Dr. Patricia Saddier 

Merck Research Laboratories 

Dr. David Salisbury 

London Department of Health 

This document has been archived for historical purposes. (7/1/2006)
Ms. Alicia Samuels 

American Cancer Society 

Ms. Debbie Saslow 

American Cancer Society 

Dr. Carlos Sattler 

Merck & Co., Inc. 

Dr. Kenneth Schmader 

Duke University/Durham Veteran’s 

Administration 

Dr. Florian Schödel 

Merck Research Laboratories 

Dr. David Schofield 

GlaxoSmithKline Pharmaceuticals 

Mr. Chris Schott 

Banc of America 

Dr. Lauri Schowalter 

GlaxoSmithKline Pharmaceuticals 

Dr. Anne Schuind 

GlaxoSmithKline Pharmaceuticals 

Mr. Jason Schwartz 

University of Pennsylvania Center for Bioethics 

Mr. Kevin Scotcher 

HSBC Securities, Inc. 

Ms. Laura Scott 

Ketchum 

Dr. Harry Seifert 

GlaxoSmithKline Biologicals 

Ms. Naomi Seiler 

House Government Reform Committee Minority 

Staff 

Dr. Lisa Shaw 

Merck & Co., Inc. 

Dr. Judith Shindman 

sanofi pasteur 

Ms. Indra Sibal 

Eternal Horizon 

Dr. Alan Sievert 

American Academy of Pediatrics 

Dr. Jeffrey Silber 

Merck & Co., Inc. 

Ms. Leah Sirkus 

Association of State and Territorial Health 

Officials 

Dr. Janet Skidmore 

Merck & Co., Inc. 

Mr. Ben Sloat 

Georgia Division of Public Health 

Mr. Parker Smith 

Parker Smith Photography, Inc. 

Ms. Susan Smith 

South Carolina Department of Health and 

Environmental Control 

Dr. Stacie Snodgrass 

Merck & Co., Inc. 

Ms. Paula Soper 

National Association of City and County Health 

Officials 

Mr. Benoit Soubeyrand 

Public 

Ms. Kim Spencer 

Generation Rescue 

Dr. Mary Staat 

Cincinnati Children’s Hospital Medical Center 

Mr. Gary Stein 

Families Fighting Flu 

Dr. Robert Steinbrook 

New England Journal of Medicine

Ms. Emily Stewart 

Planned Parenthood Federation of America, Inc. 

Ms. Katherine Stone 

Public 

Dr. Raymond Strikas 

National Vaccine Program Office 

Dr. Stacy Stuerke 

Merck Vaccine Division 

Dr. Joseph Sullivan 

Merck & Co., Inc. 

This document has been archived for historical purposes. (7/1/2006)
Dr. Ciro Sumaya 

Texas A&M Health Science Center, School of 

Rural Public Health 

Dr. Lynne Sweeney 

GlaxoSmithKline Pharmaceuticals 

Dr. Gregg Sylvester 

Merck & Co., Inc. 

Dr. Anafidelia Tavares 

The Balm in Gilead, Inc. 

Mr. Scott Thigpen 

Unify Films 

Ms. Kirsten Thistle 

APCO Worldwide, Inc. 

Mr. Lonnie Thomas 

Henry Schein, Inc. 

Dr. Michael Thoams 

Merck & Co., Inc. 

Dr. Logan Thornton 

National Institutes of Allergy and Infectious 

Diseases 

Dr. Karen Townsend 

American Academy of Pediatrics 

Ms. Monica Trigg 

Georgia Immunization Program 

Ms. Miriam Tucker 

Pediatric News

Mr. Samuel Turner 

Ropes & Gray 

Dr. James Tursi 

GlaxoSmithKline Biologicals 

Mr. William Vecino 

TDG, Inc. 

Dr. Thomas Vernon 

Public Health Consultant 

Mr. Peter Vigliarolo 

Cooney Waters 

Mr. John Vittas 

Families Fighting Flu 

Dr. Cara Vivarelli-O’Neill 

Merck Vaccine Division 

Dr. Robert Walker 

MedImmune, Inc. 

Dr. Jean Walters 

Merck & Co., Inc. 

Mr. Tim Wang 

UBS Securities 

Ms. Beth Ward 

Georgia Division of Public Health 

Ms. Tureka Watson 

McKing Consulting Corp. 

Dr. Amanda Welsh 

GlaxoSmithKline Pharmaceuticals 

Ms. Deborah Wexler 

Immunization Action Coalition 

Dr. Julia Whiting 

Public 

Ms. Margaret Williams 

APCO Worldwide 

Ms. Stacey Wilson 

Kennesaw State University, Wellstar School of 

Nursing 

Dr. Celia Woodfill 

California Department of Health Services 

Dr. Tim Xin 

USB Securities 

Dr. Elizabeth York 

GlaxoSmithKline Pharmaceuticals 

Dr. Laura York 

Wyeth Pharmaceuticals 

Dr. John Zahradnik 

sanofi pasteur 

Ms. Jennifer Zavolinsky 

Every Child By Two 

Ms. Angela Zimm 

Bloomberg News

This document has been archived for historical purposes. (7/1/2006)
Dr. Thomas Zink 

Emergent BioSolutions 

Dr. Jane Zucker 

New York City Department of Health and Mental 

Hygiene 

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Page A2.1 

ATTACHMENT 2 

Acronyms Used In This Report

AA — African American 

AAFP — American Academy of Family Physicians 

AAP — American Academy of Pediatrics 

ACHA — American College Health Association 

ACIP — Advisory Committee on Immunization Practices 

ACP — American College of Physicians 

AEs — Adverse Events 

AIAC — Adult Immunization Advisory Committee 

AIS — Adenocarcinoma In Situ

AIS — Adult Immunization Schedule 

AMA — American Medical Association 

Anti-PT — Anti-Pertussis Toxins 

AS-CUS — Atypical Squamous Cells of Undetermined Significance 

ASCO — American Society for Clinical Oncology 

ASHA — American Social Health Association 

BIG — The Balm in Gilead 

BLS — Bureau of Labor Statistics 

BRFSS — Behavioral Risk Factor Surveillance Survey 

CAIS — Childhood/Adolescent Immunization Schedule 

CDC — Centers for Disease Control and Prevention 

CIN — Cervical Intraephithelial Neoplasia 

CISA — Clinical Immunization Safety Assessment 

CLF — Celebrate Life Foundation 

CMI — Cell-Mediated Immunity 

CMS — Centers for Medicare and Medicaid Services 

COID — Committee on Infectious Diseases 

CSTE — Council of State and Territorial Epidemiologists 

CU — Columbia University 

DOD — Department of Defense 

DSMBs — Data Safety Monitoring Boards 

EPA — U.S. Environmental Protection Agency 

FAMA — Fluorescent Antibody to Membrane Antigen 

FDA — Food and Drug Administration 

FFF — Families Fighting Flu 

GBS — Guillain Barré Syndrome 

GMT — Geometric Mean Titer 

GSK — GlaxoSmithKline 

HCII — Hybrid Capture II 

HCRU — Health Care Resource Utilization 

HCWs — Healthcare Workers 

HepA — Hepatitis A 

HepB — Hepatitis B 

HHS — Department of Health and Human Services 

Hib — Haemophilus influenzae B

HICPAC — Healthcare Infection Control Practices Advisory Committee 

HIV — Human Immunodeficiency Virus 

HPV — Human Papillomavirus 

HRSA — Health Resources and Services Administration 

HZ — Herpes Zoster 

This document has been archived for historical purposes. (7/1/2006)
IgM — Immunoglobulin M 

ILI — Influenza-Like Illness 

IOM — Institute of Medicine 

IPD — Invasive Pneumococcal Disease 

ISA — Information, Support and Advocacy Center 

ISO — Immunization Safety Office 

LAIV — Live Attenuated Influenza Vaccine 

MCO — Managed Care Organization 

MCV4 — Meningococcal Conjugate Vaccine 

MMR — Measles, Mumps, Rubella 

MMRV — Measles, Mumps, Rubella, Varicella 

MMWR — Morbidity and Mortality Weekly Report

NCCS — National Coalition for Cancer Survivorship 

NCPP — National Commission on Preventive Practices 

NCRS — Nordic Cancer Registry Studies 

NHANES — National Health and Nutrition Examination Survey 

NIH — National Institutes of Health 

NIP — National Immunization Program 

NIS — National Immunization Survey 

NNDSS — National Notifiable Disease Surveillance System 

NSFG — National Survey of Family Growth 

NVAC — National Vaccine Advisory Committee 

NVPO — National Vaccine Program Office 

OB-7 — 7 Outbreak-Related States 

PCR — Polymerase Chain Reaction 

PCV23 — Pneumococcal Polysaccharide Vaccine 

PCV7 — Pneumococcal Conjugate Vaccine 

PHN — Post-Herpetic Neuralgia 

PPFA — Planned Parenthood Federation of America 

PV — Pharmacovigilance 

QALY — Quality-Adjusted Life Year 

RCA — Rapid Cycle Analysis 

RMP — Risk Management Plan 

RRP — Recurrent Respiratory Papillomatosis 

SAM — Society for Adolescent Medicine 

SPS — Shingles Prevention Study 

SSP — Sentinel Surveillance Project 

Td — Tetanus and Diphtheria 

Tdap — Tetanus, Diphtheria and Pertussis 

TIV — Trivalent Inactivated Vaccine 

TT — Tetanus Toxoid 

VA — Department of Veterans Affairs 

VAERS — Vaccine Adverse Event Reporting System 

VASP — Varicella Active Surveillance Project 

VFC — Vaccines for Children 

VRBAC — Vaccines and Related Biologics Advisory Committee 

VSD — Vaccine Safety Datalink 

VVP — Varicella Vaccination Program 

VZV — Varicella-Zoster Virus 

WHO — World Health Organization 

WIG — Women in Government 

ZUE — Zoster Utility Evaluation 

This document has been archived for historical purposes. (7/1/2006)
DEPARTMENT OF HEALTH AND HUMAN SERVICES 

CENTERS FOR DISEASE CONTROL AND PREVENTION 

NATIONAL IMMUNIZATION PROGRAM

ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES

June 29-30, 2006 

Atlanta, Georgia 

Minutes of the Meeting

The Department of Health and Human Services (HHS) and the Centers for Disease Control and 

Prevention (CDC) National Immunization Program (NIP) convened a meeting of the Advisory Committee 

on Immunization Practices (ACIP). The proceedings were held on June 29-30, 2006 at CDC’s Global 

Communications Center, Building 19, Room 232 in Atlanta, Georgia. The list of participants is appended 

to the minutes as Attachment 1. 

Opening Session 

Dr. Jon Abramson, the ACIP Chair, called the meeting to order at 8:02 a.m. on June 29, 2006 and 

welcomed the participants to the proceedings. He presented certificates and tokens of appreciation to 

four members whose terms have expired: Drs. Judith Campbell, Reginald Finger, Edgar Marcuse and 

Gregory Poland. The participants applauded the valuable and outstanding contributions the outgoing 

members made to ACIP and CDC during their service. 

Dr. Larry Pickering, the ACIP Executive Secretary, made several announcements. ACIP can be 

contacted through its e-mail address at acip@cdc.gov. The ACIP web site can be accessed at 

www.cdc.gov/nip/ACIP to obtain agendas, meeting minutes, copies of slide presentations, future meeting 

dates and up-to-date information on other ACIP activities. Time is regularly reserved on ACIP agendas 

for public comments, but formal comment periods are also scheduled during the deliberations of specific 

agenda items in limited circumstances. The next ACIP meeting will be held on October 25-26, 2006. 

Dr. Pickering noted the following changes in ACIP representation or participation for the current meeting. 

Dr. Gary Freed would begin serving as the new ACIP liaison to the National Vaccine Advisory Committee 

(NVAC) due to his recent appointment as the NVAC Chair. Ex- officio representatives for the Department 

of Defense (DOD), Food and Drug Administration (FDA), and Department of Veterans Affairs (VA) were 

absent. Replacements for the DOD and FDA ex- officio representatives were in attendance. 

Dr. Pickering reviewed ACIP’s conflict of interest and disclosure policy. Appointed members agree to 

forego participation in certain activities related to vaccines during their respective tenures in accordance 

with the conflict of interest provisions outlined in the ACIP Policies and Procedures Manual. The goal in 

appointing ACIP members is to achieve the greatest level of expertise and minimize the potential for 

actual or perceived conflicts of interest. 

CDC issued limited conflict of interest waivers for certain other interests that may enhance the expertise 

of members while serving on ACIP. The following conditions apply to members with limited waivers. 

First, members who conduct vaccine clinical trials or serve on data safety monitoring boards (DSMBs) 

ACIP Meeting Minutes June 29-30, 2006 Page 1 

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may serve as consultants and make presentations to ACIP. Second, members are prohibited from 

participating in ACIP’s deliberations or votes on issues related to those specific vaccines. Third, 

members may participate in discussions on other vaccines of the affected company, but must abstain 

from voting on vaccines manufactured by that specific company. 

The ACIP charter authorizes the Executive Secretary or designee to temporarily designate ex- officio

representatives as voting members if a quorum of eight appointed members is not available or qualified to 

vote due to financial conflicts of interest. Ex- officio representatives who are formally requested to vote 

during these circumstances will be asked to disclose any potential conflicts of interest. 

Dr. Abramson added that ACIP’s charter requires members to vote only on the safety, efficacy and costeffectiveness of vaccines. The members should not consider the existence or non-existence of federal or 

state dollars to pay for vaccines while voting. 

The following ACIP members disclosed potential financial conflicts of interest for the record. 

• Dr. Janet Gilsdorf is an uncompensated independent safety monitor for an influenza 

vaccine trial sponsored by the National Institutes of Health (NIH). 

• Dr. Gregory Poland chairs a Merck DSMB; serves as a consultant to Dyncorp and 

Vaxgen; and has engaged in preliminary discussions on clinical trials with Protein 

Sciences and PowderMed. 

• Ms. Patricia Stinchfield was a stockholder in VIRA Pharma prior to her appointment on 

ACIP. 

• Dr. John Treanor is a clinical investigator in influenza vaccine trials conducted by Merck, 

ID Biomedical, Protein Sciences and AlphaVax. 

HUMAN PAPILLOMAVIRUS (HPV) VACCINE 

The series of presentations, ACIP’s discussion and vote, and the public comments on the HPV vaccine 

are set forth below. 

Overview 

Dr. Janet Gilsdorf, the HPV Vaccine Workgroup Chair, announced that the workgroup was formed in 

February 2004 with representation by ACIP, several federal agencies and professional organizations. 

Over this time, the workgroup listened to presentations from industry, academia and other experts; 

convened monthly conference calls to review trial data; and held biweekly conference calls to formulate 

recommendations. 

FDA licensed the first HPV vaccine on June 8, 2006 for females 9-26 years of age to prevent cervical 

cancer, precancerous genital lesions and genital warts caused by HPV 6/11/16/18. Dr. Gilsdorf conveyed 

that the workgroup would now make a series of presentations, propose recommendations, and present 

the Vaccines for Children (VFC) Program resolution to facilitate ACIP’s discussions and votes on the HPV 

vaccine. 

ACIP Meeting Minutes June 29-30, 2006 Page 2 

This document has been archived for historical purposes. (7/1/2006)
GARDASIL®

 Efficacy and Safety Data 

Dr. Eliav Barr heads Merck’s HPV Vaccine Clinical Program. He presented efficacy and safety data on 

GARDASIL®

. GARDASIL® is a quadrivalent HPV vaccine that targets HPV types responsible for the 

majority of clinical HPV disease in the United States. The vaccine is available both as a vial and a 

syringe and is administered as a 0.5-mL intramuscular injection at 0, 2 and 6 months. 

The GARDASIL®

 clinical program involved 27,000 subjects in 33 countries throughout the world. The 

program enrolled two distinct cohorts: 16- to 26-year-old women and children 9- to 15-year old children. 

Subjects were enrolled regardless of baseline HPV status because the vaccine will be used without prescreening. This design was based on the recommendation by FDA’s Vaccines and Related Biologics 

Advisory Committee (VRBAC) in 2001. The primary evaluation of the vaccine focused on prophylactic 

efficacy in baseline HPV-naïve subjects, while the supplemental evaluation focused on the general 

population impact in all subjects regardless of baseline HPV status. 

The key efficacy endpoints for studies of GARDASIL®

 in women were: cervical, vulvar, and vaginal 

cancers via surrogates; the overall incidence of cervical intraephithelial neoplasia (CIN) of any grade or 

adenocarcinoma in situ (AIS); and external genital lesions caused by HPV 6/11/16/18. Immunobridging 

studies were also included in the clinical program because the vaccine will be administered to preadolescents. 

Of the Phase II/III efficacy population, the mean age was 20 years, 94% were sexually active, and 73% 

were naïve to all four HPV vaccine types. Of women with abnormal Pap test results, 58% were naïve to 

both HPV 16/18. Women with abnormal Pap test results may still benefit from protection with the vaccine. 

The vast majority of the cohort was positive to one HPV vaccine type and susceptible to the other three 

types. The percentage of the cohort that was naïve to at least three of four HPV vaccine types was 93% 

overall and 94% in North America. Merck’s clinical trial cohort and the National Survey of Family Growth 

(NSFG) showed a generally comparable distribution of sexual partners and sexual behavior. 

The prophylactic efficacy rates of GARDASIL®

 in preventing clinical HPV disease in the pre-protocol 

efficacy population are as follows: (1) 100% effective against HPV 16/18-related cervical cancer by CIN 

2/3 and AIS; (2) 100% effective against HPV 16/18-related vulvar and vaginal cancers by precancerous 

lesions; (3) 95% effective against HPV 6/11/16/18-related CIN or AIS; and (4) 99% effective against HPV 

6/11/16/18-related external genital lesions. None of the cases that occurred among subjects who 

received GARDASIL®

 were due to waning immunity because all of the cases occurred shortly after the 

completion of the vaccine regimen. 

GARDASIL®

 is best used prior to sexual debut and exposure to HPV. Impact studies of the vaccine were 

conducted in pre-adolescents, but efficacy studies were not feasible due to the difficulty in performing 

genital sampling on young girls and boys. Merck and FDA agreed that immunobridging studies could be 

conducted to extrapolate findings from females 16-26 years of age to those 9-15 years of age. The 

immunobridging studies would be used to demonstrate that anti-HPV levels induced in females 9-15 

years of age were non-inferior to those observed in the population for which efficacy was demonstrated. 

Anti-HPV responses were measured using competitive Luminex Immunoassays. These assays detect 

the subset of anti-HPV responses generated by GARDASIL®

 that compete against an antibody that is 

known to be neutralizing. The ratio of anti-HPV geometric mean titers (GMTs) between boys versus 

women and girls versus women was >1.0. These results achieved statistical criteria for non-inferiority 

and allowed an inference to be made that GARDASIL®

 is efficacious in 9- to 15-year-old individuals. In 

the adolescent population, anti-HPV levels at Month 7 and in the persistence phase were substantially 

ACIP Meeting Minutes June 29-30, 2006 Page 3 

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ACIP Meeting Minutes June 29-30, 2006 Page 4 

higher than in adults (the population in which 100% efficacy was shown). These findings provided strong 

reassurance about the magnitude and durability of efficacy of GARDASIL®

 in young adolescents. 

Population impact analyses were conducted to examine the effects of GARDASIL®

 in the general U.S. 

population of both infected and naïve women. Most older adolescents and young adult women in the 

general U.S. population are naïve to all HPV vaccine types on Day 1, but some females are infected with 

at least one HPV vaccine type on Day 1. Some females may develop disease due to HPV infection after 

Day 1. As a prophylactic vaccine, GARDASIL®

 has minimal impact on the course of infection present on 

Day 1. The efficacy of the vaccine in the general population greatly depends on baseline prevalence and 

will be reduced relative to prophylactic efficacy. 

GARDASIL®

 will prevent new HPV infections and the diseases that such infections cause. However, as 

compared to infections present at Day 1, disease caused by new HPV infections would occur later in the 

clinical trial (subjects must first acquire infection and then develop disease). GARDASIL®

 will have limited 

impact on the course of an infection present on Day 1. However, even among women who are infected 

with one HPV type, the vaccine will be highly effective in protecting against disease caused HPV vaccine 

types that are not present at Day 1. 

The population impact of GARDASIL®

 will be masked by the prevalent load of HPV infection and disease 

in the early course of the study, but efficacy will become more apparent over time. A preliminary analysis 

of prophylactic efficacy showed extremely high efficacy for each endpoint. The general population impact 

was lower, although readily apparent. The lower impact in the general population was due to cases of 

disease caused by infections present at baseline. An equal number of disease endpoints caused by 

infections present at baseline occurred in subjects who received GARDASIL®

 and subjects who received 

placebo. A shorter duration of follow-up will increase the impact of prevalent disease on the overall 

benefit of the vaccine. 

Time to event analyses showed that event rates were comparable between the GARDASIL®

 and placebo 

groups early in the first 12 months, but rates of HPV 16/18-related CIN 2/3 disease increased in the 

placebo group over time. The impact of prevalent disease was found to be less significant for genital 

warts because women with known genital warts were excluded from the clinical trial. Overall, 

GARDASIL®

 reduced the general population burden of HPV 6/11/16/18-related disease after a median of 

two years of follow-up on average. Efficacy will become more apparent and represent a more substantial 

reduction in the general load of disease over time. 

Protocol 007 was a Phase IIB quadrivalent dose ranging study and long-term efficacy evaluation. 

Because the minimal protective anti-HPV level has not been defined to date, the duration of protection 

afforded by GARDASIL®

 was measured through long-term efficacy evaluations. At five years of follow-up 

post-enrollment, prophylactic efficacy of the vaccine was high and no breakthroughs due to waning 

immunity were documented. In that study, the primary endpoint was the combined incidence of persistent 

infection, CIN, and external genital lesions caused by HPV 6/11/16/18. The persistent infection endpoint 

included detection of HPV on the last visit on record without confirmed persistence. Two cases were 

seen in the vaccine group. Subject 1 had an HPV 18 infection that occurred at months 12 and 18 and 

then resolved. Subject 2 had a positive HPV 16 test result at the last visit on record (Month 36), but 

without confirmed persistence. 

Anti-HPV levels were stable over the 60-month observation period. As a reference for vaccine induced 

anti-HPV responses, anti-HPV levels were measured in placebo subjects who were seropositive and had 

negative polymerase chain reaction (PCR) test results on Day 1. These women developed an infection 

some time after sexual debut, mounted an immune response to the infection, and cleared the infection. 

Anti-HPV levels detected at Day 1 represented residual markers of previous successful clearances of 

infection. In these previously infected women, anti-HPV levels slowly decayed over the 5-year 

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ACIP Meeting Minutes June 29-30, 2006 Page 5 

observation period. GARDASIL®

 induces high anti-HPV levels that reach a plateau. The plateau remains 

stable through month 60 and shows strong promise in terms of long-term protective efficacy of the 

vaccine. Vaccine efficacy of 96% through five years of follow-up was found to be highly statistically 

significant. 

An immune challenge study was conducted to determine the presence of immune memory responses. 

The presence of immune memory is the hallmark of hepatitis B and other long-term protective vaccines. 

An immune memory response will allow women with low, negligible or non-detectable anti-HPV levels to 

mount an extremely robust anti-HPV response and abort infections. In the immune challenge study, a 

dose of GARDASIL®

 was given to ~240 subjects in the vaccine and placebo groups who had been 

followed for five years. The results demonstrated that administration of GARDASIL®

 induced robust 

immune memory and a strong anamnestic response to HPV 6/11/16/18. 

The GARDASIL®

 clinical program will evaluate vaccine efficacy much longer than five years to mirror the 

long-term risk of women for HPV infection and disease. Many clinical study participants were enrolled in 

the Nordic region because this area has an extraordinary public healthcare infrastructure that allows for 

all Pap tests and biopsy results to be reported to the national database by identification number. Pap 

tests and biopsy results can be retrieved, followed and tested for HPV types. Sera will be available to 

evaluate anti-HPV levels because pregnant women are asked to donate a vial of sera to the registry. 

At this time, 5,500 subjects have been enrolled in the CIN 2/3 efficacy study in the Nordic region and will 

be followed over time. These subjects were vaccinated in 2002 and have been entered in a follow-up 

registry. Registry results will be reported to ACIP, CDC and regulatory agencies to determine and 

evaluate the presence of waning immunity. Merck will be in a position to provide results on the potential 

for waning immunity well in advance of the need to consider a booster strategy. A booster strategy does 

not appear to be needed based on five-year data. 

A long-term follow-up study is being conducted in adolescents to better understand the immune response 

in this population. Based on data through month 18, the levels have remained above those seen in 

adults. This population will also be followed over a long period of time. Protocol 18 includes ~1,800 

subjects 9-15 years of age who were vaccinated in 2003 with a mean age of 12 years at enrollment. 

Beginning in 2007, subjects in this cohort who reach age 16 will enter an efficacy phase and undergo 

genital sampling. Protocol 18 results will be periodically reported to CDC, FDA and other regulatory 

agencies to demonstrate the long-term immunity and effectiveness of the vaccine in both adolescent boys 

and girls in this cohort. 

The clinical trial program places strong emphasis on evaluating the safety profile of GARDASIL®

. Of 

~21,464 subjects, ~11,000 received detailed safety follow-up and the remainder received serious adverse 

experiences in medical history and pregnancy follow-up. The incidence of overall adverse events (AEs), 

injection-site AEs, and low-grade fevers >100°F was slightly higher in the GARDASIL®

 group compared to 

the placebo group. Systemic AEs were comparable between the two groups. Serious AEs and 

discontinuation due to adverse experiences were extremely rare. 

GARDASIL®

 is a unique vaccine due to its administration to girls and women of child-bearing age. An 

extremely careful pregnancy evaluation was incorporated into the clinical trials program to monitor 

pregnancies. In the overall clinical database, 11% of the population became pregnant during the course 

of follow-up and some subjects had multiple pregnancies. 

As of November 11, 2005, ~500 pregnancies were still ongoing and outcomes were known for ~2,000 

pregnancies. Live births and fetal losses were comparable between the 1,244 pregnancies in the 

GARDASIL®

 group and the 1,272 pregnancies in the placebo group. The GARDASIL® group had a lower 

incidence of spontaneous miscarriage, lower incidence of elective termination, and higher incidence of 

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ACIP Meeting Minutes June 29-30, 2006 Page 6 

live births. However, these differences compared to the placebo group were small. The overall rates of 

congenital anomalies were also comparable among the vaccination groups. 

Further analyses were conducted in two strata of pregnancies: pregnancies whose estimated onset 

occurred within 30 days of administration of GARDASIL®

 and those pregnancies whose estimated onset 

occurred beyond 30 days of administration of GARDASIL®

. In pregnancies whose estimated onset 

occurred within 30 days of administration of a dose of GARDASIL®

/placebo, five cases of congenital 

anomalies were observed all in the group that received GARDASIL®

. On the other hand, among 

pregnancies whose estimated onset occurred beyond 30 days of administration of a dose of 

GARDASIL®

/placebo, fewer congenital anomaly cases were observed in subjects who received 

GARDASIL®

 compared to placebo subjects. 

A panel of four teratologists from around the world examined these data in a blinded fashion and 

unanimously agreed that the congenital anomalies were highly unlikely to be associated with the 

administration of GARDASIL®

. The opinions of the teratologists are further supported by pre-clinical 

developmental and reproductive toxicology studies that showed high doses of GARDASIL®

 had no impact 

on pregnancy outcomes and fertility. GARDASIL®

 is one of the first vaccines to have been granted a 

category B designation from FDA. 

The key highlights and findings of the GARDASIL®

 clinical program are as follows. Prophylactic 

administration of GARDASIL®

 is highly effective in preventing cervical and genital disease caused by four 

HPV vaccine types based on a clinical trial of 27,000 women and five-year follow-up data. A long-term 

program was established to specifically focus on the duration of efficacy. Efficacy without breakthrough 

infections due to waning immunity has been demonstrated through year 5. Anti-HPV levels are stable at 

year 5 with extremely strong immune memory responses present. These data are solid indicators for the 

long-term protective efficacy of GARDASIL®

. 

Sentinel cohorts were established to examine the long-term efficacy of the vaccine. Data on waning 

immunity will be produced well in advance of the need to consider a vaccination policy. GARDASIL®

 is 

generally well-tolerated in females 9-26 years of age. The vaccine contains certain components that are 

well known and understood to be safe and effective long term. GARDASIL®

 demonstrated slight 

increases in injection-site AEs and low-grade fevers compared to placebo, but the rates of serious AEs 

and discontinuation were extremely low. 

GARDASIL®

 will significantly impact a major public health problem in the United States and the burden of 

disease caused by HPV that results in precancerous lesions for cervical, vulvar and vaginal cancers. The 

vaccine has an excellent safety profile and demonstrated a population-based reduction in cervical precancers and external genital lesions. Merck believes that GARDASIL®

 has a strong public health impact. 

Dr. Barr provided additional details about the safety and efficacy of GARDASIL®

 in response to ACIP’s 

questions. 

• The most common AEs reported in the clinical trial were headache, dysmenorrhea and 

related symptoms, sore throat, and nasopharyngitis and other influenza-like conditions. 

These AEs were comparable between the GARDASIL®

 and placebo groups based on the 

subject’s individual perception of a “mild,” “moderate” or “severe systemic” AE. The 

overall AE rates were lower in the younger age group because dysmenorrhea and other 

types of symptoms were less frequent in this population. 

• Of the 27,000 subjects, ~4,072 9-17 years of age received GARDASIL®

. 

• Similar to GARDASIL®

, an age versus peak anti-HBs response was also seen with the 

hepatitis B (HepB) vaccine. 

This document has been archived for historical purposes. (7/1/2006)
• Merck conducted a co-administration study of GARDASIL®

 with the HepB vaccine. The 

adverse experience profile and immune response to both vaccines were found to be 

generally comparable. Merck is planning to conduct new co-administration studies of 

GARDASIL®

 with ADACELTM and Menactra®. These data are expected to be available in 

late 2007. 

• Merck completed two analyses to evaluate whether removal of common HPV types will 

result in replacement with non-vaccine HPV types. An HPV 16 vaccine trial showed 

100% efficacy. Incidence rates for HPV 6/11/18 infections were comparable between 

vaccination groups over four years. Similarly, the incidence of CIN caused by HPV types 

other than 6/11/16/18 was analyzed in the general population in Phase III studies. No 

difference was seen between the vaccination groups. Thus, there is no evidence for 

replacement. Merck will continue this study in long-term surveillance. 

• Merck is collaborating with the government of Norway in the establishment of a 

vaccination registry of each subject in the country. Merck will use these data in its 

pharmacovigilance (PV) activities to analyze trends in attack rates over time for HPV 

types not included in GARDASIL®

. HPV biology does not indicate that replacement will 

occur because the rate of infection is higher with a second type if infection is already 

present with one type. 

GARDASIL® Risk Management Plan (RMP)

Dr. Adrian Dana, of Merck & Co, Inc., presented the GARDASIL® RMP. The RMP will be structured in 

three major areas. First, the safety specification will summarize the safety database, safety knowledge, 

data gaps and known risks for the product. Second, the PV plan will outline approaches that will be taken 

to follow the safety of the product in the future; describe routine PV practices; and delineate action plans 

for specific safety concerns of the product. Third, a risk minimization plan will be developed if necessary, 

but is not expected to be needed for GARDASIL®

. 

Of >21,464 subjects enrolled in the clinical development program, >11,700 received GARDASIL®

. No 

significant signals were identified, but adverse experiences not seen in clinical trials may become evident 

as the product is used more widely in the post-marketing setting. The RMP includes a post-marketing 

safety surveillance study and the Nordic Cancer Registry Studies (NCRS). The four components of the 

routine PV and action plans in the GARDASIL®

 RMP are detailed below. 

First, exposures during pregnancy will be monitored. FDA gave GARDASIL®

 a category B product 

labeling because animal reproductive toxicology studies revealed no adverse effects, but no controlled 

trials have been performed on pregnant women. No signal was seen with respect to pregnancy 

outcomes in the clinical development program. Merck recommends deferral of vaccination if pregnancy 

occurs. 

Pregnancy exposures serve as a rationale for intensified efforts to obtain outcome information and other 

safety data. Spontaneously reported pregnancy exposures will be routinely analyzed (routine PV). 

Additionally, Merck subscribes to the Swedish birth register of pregnant women for the entire country of 

Sweden. Merck obtains drug exposure data from the registry and annual information on women who 

were exposed during pregnancy in Sweden. 

Merck is currently developing a pregnancy registry for the United States, France and Canada for 

enhanced surveillance of spontaneously reported pregnancy exposures. Data from the registries will be 

continuously reviewed. Reports will be prepared and submitted annually to regulatory and public health 

ACIP Meeting Minutes June 29-30, 2006 Page 7 

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ACIP Meeting Minutes June 29-30, 2006 Page 8 

agencies and healthcare practitioners who report exposures to the registry. The cumulative annual 

reports can serve as a foundation for exposed women to receive counseling. 

Merck will conduct an observational post-marketing safety surveillance trial in a managed care 

organization (MCO) setting. The study will focus on pregnancy exposures that occur during the trial to 

provide a descriptive epidemiology of exposures. The government of Norway committed to establishing 

an HPV vaccine registry for the entire country. Merck will use data from the HPV vaccine registry and 

existing birth registers in Norway to analyze pregnancy exposures and outcomes (this is part of the 

NCRS). 

Second, replacement with non-vaccine viral types will be monitored due to the theoretical concern that 

vaccination against some types will leave a niche for other types to emerge. This theory is influenced by 

the pathogenicity of the organism and the virulence of the specific types. No biologic data have been 

produced to support this theory and no evidence of replacement has been seen in clinical trials to date. 

Infection with one HPV type is actually a risk factor for infection with other types. 

The NCRS will be designed to monitor replacement in the future. The Protocol 15 cohort has been 

vaccinated and will be followed in the future to determine if these subjects tend to develop higher rates of 

infection with other types. The HPV vaccine registry in Norway will also be analyzed to monitor 

population trends over time and determine whether replacement becomes an issue. 

Third, long-term effectiveness and immunogenicity will be monitored. The five-year data on GARDASIL®

do not show breakthroughs due to waning immunity and demonstrate that the vaccine has the ability to 

induce long-lasting immune memory. However, the duration of protection and the need for a booster are 

unknown at this time. The action plan for this component includes reviews of NCRS data; long-term 

follow-up of the Protocol 15 cohort to monitor effectiveness and immunogenicity; and a similar follow-up 

study with the adolescent Protocol 18 cohort. 

Fourth, unanticipated safety signals will be detected. For short-term safety, an observational postmarketing safety surveillance study will be conducted in an MCO setting in the United States among 

44,000 vaccinees. Safety issues that occur 60 days following a dose will be analyzed. Thyroiditis, 

rheumatoid arthritis and other autoimmune disorders will be analyzed six months following a dose. 

For long-term safety, NCRS data will be reviewed. The Protocol 15 cohort will be followed over a long 

period of time to monitor long-term effectiveness, immunogenicity and safety. The incidence of major 

diseases and other trends will be compared between the study cohort and the general population using 

existing disease registries in the Nordic region. Overall, Merck is committed to analyzing GARDASIL®

and following its impact long term. 

Drs. Dana and Barr provided additional details about the GARDASIL®

 RMP in response to ACIP’s 

questions. 

• Merck has several reasons to be confident about its ability to make comparisons between 

the Nordic and U.S. populations. The large population-based registries in the Nordic 

region provide a unique opportunity to obtain much more complete data for improved 

evaluation and follow-up. Epidemiologic studies in the Nordic region indicate that the 

distribution of HPV types and disease progression is similar to other areas in Europe and 

the United States. The Nordic population has HPV demographics, attack rates and 

sexual behavior patterns that are comparable to the U.S. population. The Nordic region 

will serve as an excellent area to analyze and follow any signals that are generated. 

This document has been archived for historical purposes. (7/1/2006)
• Merck will not solely rely on data from the Nordic region. The adolescent cohort that will 

be followed long-term represents 50% of subjects from the United States. The short-term 

safety study with 44,000 subjects will be conducted in the United States. 

• The clinical trial database includes data that strongly support the use of GARDASIL®

 in 

various ethnic groups. Large Hispanic and African American (AA) cohorts were 

evaluated. The five-year efficacy data were primarily from subjects in Brazil and 

Scandinavia. Merck is committed to analyzing the data with respect to racial/ethnic and 

country-specific differences. 

• The GARDASIL®

 clinical trial program did not demonstrate ethnic differences in the 

efficacy of anti-HPV levels. Populations in the Nordic region are more homogeneous 

than those in the United States, but the Nordic cohort was stratified by disease rates, comorbidities, behavior patterns and other non-ethnic factors. 

GARDASIL® Post-Marketing Safety Surveillance

Dr. John Iskander, of the CDC Immunization Safety Office (ISO), described CDC’s vaccine safety 

monitoring plan for the quadrivalent HPV vaccine. ISO partners with FDA, MCOs and other private-sector 

companies, academic medical centers and international collaborators in conducting post-marketing safety 

surveillance activities for newly licensed vaccines. The Vaccine Adverse Event Reporting System 

(VAERS) is a national passive surveillance system for reporting AEs and is co-managed by CDC and the 

FDA. VAERS has under-reported data and an inability to determine causal relationships between 

vaccines in most reports. Despite these limitations, VAERS maintains a solid track record as a 

hypothesis-generating system. 

VAERS is designed to detect rare or previously unknown AEs that may warrant further detailed study and 

identify potential risk factors for adverse reactions. The rationale for the VAERS design is because prelicensure trials are of limited size and typically exclude special populations that may subsequently receive 

the vaccine following licensure. Federal regulations define “serious AEs” as those involving 

hospitalization, death, life-threatening illness, disability, and congenital anomalies or certain other serious 

medical conditions. CDC, FDA and subject-matter experts review serious AEs reported to VAERS and 

follow-up these reports after obtaining additional medical records. 

The Vaccine Safety Datalink (VSD) is a network of MCOs that participates in a large linked database. 

VSD conducts vaccine safety hypothesis testing studies and performs active surveillance of AEs for 

newly licensed and other vaccines. Rapid cycle analysis (RCA) is a new VSD component that involves 

reviewing VSD data at selected sites on a weekly basis, identifying AEs of interest, and determining 

whether predetermined statistical thresholds were exceeded. 

For the quadrivalent HPV vaccine, the RCA will focus on cardiovascular, allergic and clinical issues 

identified pre- or post-licensure. Women who received the vaccine will be followed for up to 30 days 

using automated linked data. Chart review for diagnosis verification will be conducted as needed. 

Sequential probability ratio testing will be used to compare expected and actual outcome rates. 

The development of an analytic data file of pregnancy outcomes for VSD is underway to compliment data 

from VAERS and Merck’s pregnancy registry. Women who are vaccinated during pregnancy or become 

pregnant following HPV vaccine or other vaccines of interest will be actively monitored. The pregnancy 

outcomes of interest include spontaneous and elective pregnancy terminations, stillbirths, live births and 

congenital anomalies. 

ACIP Meeting Minutes June 29-30, 2006 Page 9 

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Potential Cost-Effectiveness of HPV Vaccination in the United States 

Dr. Harrell Chesson, of the CDC Division of STD Prevention, presented data to demonstrate the potential 

cost-effectiveness of HPV vaccination in the United States. Two types of models have been used in the 

HPV vaccine cost-effectiveness literature. Markov models are typically used to model the natural history 

of HPV infection, but may understate the benefits and cost-effectiveness of vaccination. These models 

do not include transmission effects or herd immunity. Dynamic models may be more realistic because 

HPV transmission is modeled. However, these models may introduce additional uncertainty due to the 

inclusion of transmission probabilities, sexual mixing patterns and other factors. 

Of three published studies that utilized Markov models to estimate the cost-effectiveness of HPV 

vaccination in the United States, two included current cancer screening in the United States and focused 

on cost-effectiveness in terms of cost per quality-adjusted life years (QALY) gained. The Goldie study 

was published in 2004 with the following base case assumptions. The vaccine would have 90% efficacy 

against HPV 16/18. Females would be vaccinated at 12 years of age with 100% vaccination coverage. 

The duration of the vaccine would be lifetime and the cost would be $377 per series. Under these base 

case assumptions, the cost per QALY for female-only vaccination would be $24,300 in the Goldie study. 

The Sanders model was published in 2003 with the following base case assumptions. The vaccine would 

have 75% efficacy against all high-risk HPV types. Females would be vaccinated at 12 years of age with 

70% vaccination coverage. The duration of the vaccine would be ten years plus an additional ten years 

with a booster. The cost would be $300 per series and an additional $100 for the booster. Under these 

base case assumptions, the cost per QALY for female-only vaccination would be $22,800 in the Sanders 

study. 

In sensitivity analyses of published Markov models, cost-effectiveness estimates were sensitive to the 

duration of vaccine efficacy and cervical cancer screening factors, such as the frequency and age of 

initiation of screening. The cost-effectiveness estimates were less sensitive to reasonable changes in 

natural history parameters and screening test characteristics. 

Two studies utilized dynamic models to estimate the cost-effectiveness of HPV vaccination. The Taira 

study was published in 2004 with the following base case assumptions. The vaccine would have 90% 

efficacy against HPV 16/18. Females would be vaccinated at 12 years of age with 70% vaccination 

coverage. The duration of the vaccine would be ten years plus an additional ten years with a booster. 

The cost would be $300 per series and an additional $100 for the booster. Under these base case 

assumptions in the Taira study, the vaccination of females 12 years of age would cost $14,600 per QALY 

compared to no vaccination. 

The ongoing Merck study has the following base case assumptions. The vaccine would have 90% 

efficacy against infection and 100% efficacy against disease for HPV 6/11/16/18. Females would be 

vaccinated <12 years of age with a catch-up scenario at 12-24 years of age. Vaccination coverage would 

be 70%, the duration of the vaccine would be lifetime, and the cost would be $300 per series. Under 

these base case assumptions, the vaccination of females 12 years of age and the addition of a catch-up 

strategy for females 12-24 years of age compared to screening without vaccination would both be costsaving (<$0 per QALY) in the Merck study. 

The approach of adding a catch-up strategy dominated the vaccination-only strategy of females 12 years 

of age in the Merck study. Unpublished Merck data show that in the long run, the reduction in cervical 

cancer incidence attributable to HPV 16/18 would be the same regardless of catch-up vaccination. 

However, reductions in cervical cancer incidence would be seen ~10 years sooner with a catch-up 

vaccination. Merck also designed an alternative scenario to conduct a sensitivity analysis of its model. 

ACIP Meeting Minutes June 29-30, 2006 Page 10 

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ACIP Meeting Minutes June 29-30, 2006 Page 11 

Under these assumptions, the vaccine would cost $360 per series and have a ten-year duration of 

protection with 50% coverage. The utility loss from HPV-related health outcomes would be reduced by 

33%. A time horizon of 25-100 years would be used to calculate the cost and benefits of vaccination. 

Compared to screening and no vaccination, the cost per QALY associated with the vaccination-only 

strategy of females 12 years of age increased from ~$27,000->$70,000 as the time horizon decreased 

from 100-25 years. The cost for the catch-up strategy increased from ~$12,000-~$25,000 over the same 

time horizons. The approach of adding a catch-up strategy dominated the vaccination-only strategy. 

Cost-effectiveness estimates for the catch-up strategy were less sensitive to changes in the time horizon 

as those for the strategy of vaccinating only females 12 years of age. The findings demonstrate that the 

HPV vaccine will be a long-term investment with benefits increasing over time. 

Merck also changed its assumptions to mirror Markov models. The impact of the vaccine on HPV 6/11 

and transmission effects resulting in herd immunity were removed. Efficacy of 90% against HPV infection 

and disease was assumed. The outcomes of this analysis were similar to the Markov model estimates. 

The cost-effectiveness of vaccinating females 12 years of age compared to no vaccination was $21,400 

per QALY at a vaccine series cost of $400. 

CDC developed a detailed spreadsheet to estimate the cost and benefits of vaccination over a 50-year 

time period. HPV outcomes were estimated based on age-specific incidence rates in the United States. 

The calculations were made with the following assumptions. Females 12 years of age would be 

vaccinated each year with 70% coverage. Efficacy of the vaccine would be 100% with lifetime duration of 

protection against the four HPV types. CDC’s base case assumptions were modified to compare with the 

other models and a 50-year time horizon was used. Cost and QALY estimates for HPV-related health 

outcomes were obtained from the literature. 

No transmission effects were assumed in the base case analysis, but a transmission scenario was 

developed. The reduction in disease burden among unvaccinated females was assumed to be a function 

of the percentage of those vaccinated in a five-year age group. The reduction in genital warts among 

males was assumed to be 75% of the decrease in females. 

A small reduction in the HPV burden was seen in year 5 compared to year 50. The reduction in disease 

burden was greater in each of the 50 years when transmission effects were included to represent herd 

immunity impacts. CDC modified the spreadsheet to mirror vaccine efficacy rates and vaccine costs of 

the Goldie, Sanders, Merck and Taira studies. CDC’s estimates of the cost per QALY of routine 

vaccination were similar to these models when the base case assumptions were changed. 

CDC acknowledges the substantial variations in cost-effectiveness that can occur when base case 

parameter values and assumptions are modified. For example, the vaccine was not found to be costsaving when base case assumptions were slightly modified with a 50-year time horizon. CDC also 

realizes that the limitations of models must be considered when making cost-effectiveness estimates. 

Substantial uncertainty exists about the transmission dynamics of HPV, duration of immunity, role of 

natural immunity and other factors. Models cannot address all potential effects of vaccination, such as 

the decreased positive predictive value of the Pap test; AEs following vaccination; sexual, health-seeking 

and other behaviors; and other HPV-related cancers. 

CDC reached the following conclusions in reviewing cost-effectiveness studies of HPV and estimating the 

cost and benefits of vaccination. The vaccination of females 12 years of age was estimated to cost 

~$23,000 per QALY compared to screening and no vaccination based on a Markov model of a bivalent 

vaccine. Cost-effectiveness estimates were more favorable toward vaccination when protection against 

HPV 6/11 and herd immunity impacts were considered. 

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Preliminary results from the Merck study suggest that catch-up vaccination of females 12-20 years of age 

would be more cost-effective than a vaccination-only strategy of females 12 years of age. Costeffectiveness estimates would be more favorable toward vaccination as the time horizon increases and 

fairly consistent across different models when key assumptions are similar. Cost-effectiveness estimates 

would substantially vary as model assumptions are modified. The vaccination of females can be costsaving under certain assumptions. 

Drs. Abramson and Lieu emphasized the critical need to apply lessons learned with the HepB vaccine to 

HPV. Based on experiences with the HepB vaccine, the failure of many adolescents to present for all 

three doses of the HPV vaccine should be explicitly incorporated into cost-effectiveness models. Dr. Lieu 

found the herd immunity models to be impressive, but she noted that the ability to achieve high coverage 

rates to obtain herd immunity is unknown. The cost-effectiveness of catch-up vaccination is also 

uncertain due to unanswered questions related to herd immunity. 

Drs. Chesson, Barr and Erik Dasbach of Merck provided additional details about the potential costeffectiveness of HPV vaccination in the United States in response to ACIP’s comments and questions. 

• Lower vaccine efficacy and decreased cost-effectiveness can be assumed if only one or 

two doses of the three-dose HPV vaccine series are administered. 

• Merck modelers reported that the cost-effectiveness of catch-up vaccination was under 

$50,000 per QALY even when excluding the benefits of herd immunity and the benefits of 

protection against HPV 6/11. 

• It was noted that a set of replacement handouts for the cost-effectiveness summary had 

been distributed to ACIP. 

• Merck has not analyzed the cost-effectiveness of catch-up vaccination followed by a 

vaccination strategy of females 11-12 years of age. 

• Merck plans to conduct studies on infants in the future, but administering GARDISIL®

 to 

babies is premature at this point. Merck is extremely confident about the long-term 

efficacy of the vaccine in adolescents based on five-year data, but a much longer 

duration of efficacy is needed between the time an infant is vaccinated and reaches the 

risk period. 

• All of the cost-effectiveness models accounted for age-specific event rates and the 

duration of efficacy because HPV is a common infection and sexually active women 

remain at risk regardless of age. Event rates in the United States continue to be 

substantial for women >30 years of age. A new peak is now being seen among women 

in older age groups. 

• The transmission models account for fewer males acquiring HPV if the prevalence of 

HPV is lower in female sex partners. In this scenario, both male-to-female and female-tomale transmission would be reduced. 

Public Comment Period 

Dr. Mark Gorman, of the National Coalition for Cancer Survivorship (NCCS), made the following 

comments for ACIP’s consideration. NCCS urges ACIP to recommend optimal usage of the HPV 

vaccine. The NCCS President attended the May 2006 VRBPAC meeting to endorse FDA approval of the 

HPV vaccine with coverage to as many young persons as possible consistent with available data. 

NCCS looks forward to the imminent coverage of the vaccine to young males to more efficiently interrupt 

transmission of the HPV virus. The vaccine can prevent thousands of cases of cervical, vaginal, vulvar, 

anal, penile, and head and neck cancers. NCCS encourages ACIP to take advantage of a special and 

ACIP Meeting Minutes June 29-30, 2006 Page 12 

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ACIP Meeting Minutes June 29-30, 2006 Page 13 

unique opportunity to make available a preventive and cost-effective intervention that will bypass suffering 

associated with current cancer treatment. ACIP should also recommend inclusion of the HPV vaccine in 

the VFC Program to ensure that the greatest number of at-risk young persons receive the vaccine at the 

earliest possible time. 

Ms. Emily Stewart, the Regulatory and Policy Analyst for Planned Parenthood Federation of America 

(PPFA), made the following comments for ACIP’s consideration. The combination of the HPV vaccine, 

cervical cancer screening programs, and early detection and treatment has an enormous potential to 

impact public health. Lessons learned from successful immunization strategies should be reviewed and 

access to the HPV vaccine should be a public health priority. 

ACIP should recommend routine immunization and inclusion of the vaccine in the VFC Program to ensure 

the widest possible access and coverage. ACIP should also recommend administration of the vaccine to 

females 11-12 years of age; all females up to 26 years of age who missed vaccination; and a 

complimentary vaccination strategy for males as more evidence is generated. 

The public health impact of the HPV vaccine must not be derailed by false ideological propaganda. PPFA 

is counting on ACIP to make rational decisions based upon science and public health. The inability of 

prevention to promote sexual activity is well established. Moreover, cancer prevention is preferable to 

cancer treatment. 

Dr. Denise Ross, the Chief Medical Officer of AmeriChoice, made the following comments for ACIP’s 

consideration. AmeriChoice serves >1.3 million government beneficiaries in the healthcare system in 13 

states. Of all AmeriChoice clients, ~50% are children who would benefit from the HPV vaccine. Cervical 

cancer is the leading cause of morbidity and mortality among women in the United States. Cervical 

cancer caused by HPV disproportionately affects AA and Hispanic women at rates that are roughly 

double than the general population. 

Data indicate that widespread immunization of the HPV vaccine could prevent 70% of cervical cancers 

associated with HPV 16/18, a substantial proportion of vaginal and vulvar cancers, and genital warts. 

AmeriChoice places tremendous emphasis on immunization, promotes other prevention strategies, and 

strongly supports the use of the HPV vaccine in its health plans. ACIP’s recommendations for coverage 

should be as broad as FDA’s recent approval of the vaccine. 

AmeriChoice’s position is that emphasis on the importance of the HPV vaccine by health plans, 

physicians and parents may increase the number of adolescents who are immunized with other 

recommended vaccines. This approach may also expand the number of adolescents who present for 

preventive care visits. AmeriChoice is committed to strengthening its efforts to reach at-risk adolescents 

as this population reaches an age when sexual activity may commence. The HPV vaccine represents a 

notable advance in preventing disease through immunization, particularly cancers that cause a 

tremendous amount of suffering among minority and other women in the United States. AmeriChoice 

urges ACIP to recommend widespread use of the HPV vaccine. 

Dr. Anafidelia Tavares, Director of Women’s Health at The Balm in Gilead (BIG), made the following 

comments for ACIP’s consideration. AA women have the highest rate of cervical cancer mortality of any 

group of women in the United States. BIG makes sustained and concerted efforts to address these 

disparities through the following activities. The health status of persons of African descent is improved by 

building capacity of the AA faith community to address life-threatening diseases. A cervical cancer 

initiative was developed to educate AA women about cervical cancer, HPV and the need for screening. A 

partnership was formed with three AA religious denominations with a combined reach of >6 million 

women. 

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ACIP Meeting Minutes June 29-30, 2006 Page 14 

Research has shown that uninsured and vulnerable women have the highest burden of disease from 

cervical cancer. FDA data have demonstrated that the HPV vaccine is safe and efficacious. The 

prevention of cervical cancer cases in the future will depend on access to the HPV vaccine for all women. 

BIG urges ACIP to recommend the most comprehensive indications for use of the vaccine. ACIP’s 

recommendations will drive access to the vaccine through private insurers and the VFC Program. ACIP’s 

recommendations will also influence outcomes to the most privileged and vulnerable women. BIG 

encourages ACIP to recommend wide use of the HPV vaccine to stem the tide of cervical cancer and 

ensure that the life-saving promise of the vaccine reaches all women. 

Ms. Deborah Arrindell, Vice President of Health Policy for the American Social Health Association 

(ASHA), made the following comments for ACIP’s consideration. ASHA has a 92-year history of 

attempting to eliminate sexually transmitted diseases and associated outcomes for individuals, families 

and communities. ASHA is confident that ACIP has thoroughly considered the science and public health 

advantages of the HPV vaccine. The vaccine is an exciting and critically important tool to prevent cervical 

cancer in the United States and throughout the world. 

ASHA urges ACIP to take three critical actions in its decision-making process. First, the HPV vaccine 

should be recommended for as broad an age group as permitted by FDA. Second, providers should be 

strongly encouraged to inform all patients that comprehensive cervical cancer screening and follow-up 

programs must be continued even with the HPV vaccine. GARDASIL®

 has proven to be >99% effective 

against HPV types that cause 70% of cervical cancers. Continued screening and HPV testing will be 

essential to detect the remaining 30% of cancers from other high-risk types. Third, national outreach 

should be promoted to ensure that underserved women have access to the HPV vaccine through VFC 

and other federally funded public health programs. 

ASHA is particularly concerned about access to the vaccine among at-risk females. HHS has 

acknowledged that cervical cancer rates are sentinel markers for larger systemic healthcare concerns. 

Access of the vaccine among groups with the highest burden of cervical cancer must be a public health 

priority. 

ASHA is a member of a newly formed partnership of >30 national organizations. The mission of the 

network is to end cervical cancer and ensure the immediate inclusion of vaccines that prevent cervical 

cancer into routine health care for women. To fulfill its mission, the network will focus on HPV and 

cervical cancer education; health disparities that impede access to vaccines and other routine preventive 

care; coverage and reimbursement; and the need for an infrastructure for adult immunization programs. 

ASHA is prepared to support widespread availability and acceptability of cervical cancer vaccines. 

Dr. Otis Brawley is a Professor of Medical Oncology and Epidemiology at the Emory University Cancer 

Center. He represented the American Society for Clinical Oncology (ASCO) and made the following 

comments for ACIP’s consideration. Data have shown that the HPV vaccine prevents cervical cancer 

and is 100% effective in preventing vaginal and vulvar cancers associated with certain HPV types. 

ASCO strongly believes that ACIP’s general and VFC recommendations should provide for the widest 

possible coverage of immunization with the HPV vaccine among at-risk young persons. The 

disproportionate impact of cervical cancer on AA and Hispanic women provides ACIP with a strong 

rationale to issue a generous recommendation on comprehensive VFC coverage. At a minimum, 

recommended coverage should be as broad as the FDA-approved labeling of females 9-26 years of age. 

ASCO acknowledges the need to continue screening. 

ASCO strongly supports the immunization of males because this strategy will optimize the potential of the 

vaccine and promote a strong message of shared male-female responsibility for prevention. Lessons 

learned with the rubella vaccine demonstrate that female-only immunization is not a successful approach. 

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ACIP Meeting Minutes June 29-30, 2006 Page 15 

Data on males should be expeditiously reviewed and recommendations for male immunization should be 

adopted accordingly. ASCO believes recommendations on the use of the HPV vaccine should be 

expanded beyond the current FDA approval to include immunizations of males if the data support this 

approach. 

Ms. Michelle Hannah, founder of Celebrate Life Foundation (CLF), made the following comments for 

ACIP’s consideration. Ms. Hannah’s mis-diagnoses and three surgeries led to her personal mission, 

purpose, commitment and passion to provide education, promote awareness about HPV and eliminate 

cervical cancer. She is also making these efforts to ensure her young daughter does not face the same 

struggle in the future. 

CLF is concerned that the HPV vaccine will not be available to low-income, inner-city and uninsured 

populations. CLF is partnering with Howard University and the Washington Hospital Center to address 

these issues and identify solutions. However, ACIP should also consider these concerns in formulating 

recommendations on the HPV vaccine. 

Ms. Gloria Lawlah is the State Senator for Maryland. She represented Women in Government (WIG) 

and made the following comments for ACIP’s consideration. The elimination of cervical cancer is one of 

WIG’s top priorities. WIG’s “Challenge to Eliminate Cervical Cancer Campaign” has resulted in state 

legislators introducing bills and resolutions targeting cervical cancer prevention in 45 states. Since 2004, 

39 of these measures have been enacted. FDA’s recent approval of the HPV vaccine is a tremendous 

milestone and an important step in ensuring that no more women die of cervical cancer. 

WIG acknowledges the critical need for the HPV vaccine to be made available to all recommended age 

groups regardless of socioeconomic status. WIG urges ACIP to recommend coverage for all FDAapproved age groups and include the vaccine in the VFC Program. WIG’s network of state legislators 

around the country is ready to support a public health effort to ensure that all age-appropriate females 

receive the HPV vaccine regardless of race, ethnicity or socioeconomic status. 

WIG’s position is that HPV vaccines should be included in comprehensive cervical cancer prevention 

programs with advanced and medically appropriate screening and testing methods. WIG’s network of 

state legislators will await ACIP’s recommendations on the HPV vaccine and make efforts to reach the 

mutual goal of eliminating cervical cancer for all women in the United States. 

Mr. Michael Green is the founder and Executive Director of the International Recurrent Respiratory 

Papillomatosis (RRP) Information, Support and Advocacy Center (ISA). He made the following 

comments for ACIP’s consideration. HPV 6/11/16/18 cause RRP in addition to genital warts and cervical 

cancer. RRP is a disease in which tumor-like lesions grow on the larynx, trachea and lungs. Untreated 

lesions can convert to cancer, cause suffocation and eventually result in death. The burden of RRP can 

equal tens of millions of cases in the United States alone. 

RRP can be passed from pregnant women with HPV to their children, but the disease can also affect 

adults. RRP is associated with a tremendous emotional burden and unrelenting guilt of mothers who 

pass the disease to their children. These children must undergo hundreds of surgeries to maintain open 

airways. Dr. Keerti Shah is a world-renowned expert on HPV and RRP and recently stated that 

GARDASIL®

 will prevent RRP. During its decision-making process, ACIP should consider that 

GARDASIL®

 prevents RRP, head and neck cancers, and cervical cancer. 

ACIP should recommend wide use of the vaccine for females 9-29 years of age and uninsured children in 

the VFC Program. This recommendation will increase access to the vaccine through both public health 

programs and private health plans. ISA is also requesting that ACIP’s broad-based recommendations 

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include males in addition to females. The immunization of adolescent males with the HPV vaccine will 

prevent the development of RRP in this population. 

Mr. Green described the impact of non-cervical HPV disease on Ms. Kathy Blankenship, ISA’s research 

investigator. Ms. Blakenship can only speak through a computer and electronic larynx. The quality of her 

life was severely affected in 2001 by a series of HPV-related tumors and cancers. HPV affects males and 

females of all ages. The disease causes RRP and 25% of all head and neck cancers in addition to 

cervical cancer. 

The World Health Organization (WHO) identified HPV vaccination as one of four public health strategies 

that could reduce the world cancer burden by up to 33%. ACIP should consider this powerful message 

when formulating its recommendations on the HPV vaccine. ACIP’s recommendations will have a strong 

influence on insurance companies. The cost of prevention is minuscule compared to the expenses 

associated with cancer treatment. 

Proposed Recommendations for the Quadrivalent HPV Vaccine 

Dr. Lauri Markowitz is the CDC lead on the HPV Vaccine Workgroup. She presented the workgroup’s 

proposed language, supporting data and rationale in formulating recommendations for the quadrivalent 

HPV vaccine. FDA licensed the quadrivalent HPV vaccine on June 8, 2006 for use in females 9-26 years 

of age for prevention of certain diseases caused by HPV 6/11/16/18. The workgroup is soliciting ACIP’s 

votes on four recommendations. 

Recommendation 1 is for routine vaccination. “ACIP recommends routine vaccination of females 11-12 

years of age, with three doses of the quadrivalent HPV vaccine. The vaccine series can be started as 

young as nine years of age at the discretion of the provider.” The workgroup’s rationale and data to 

support routine vaccination are outlined below. 

The incidence of infection with one or more serotypes of HPV is high, and the risk to the individual of 

infection increases rapidly following onset of sexual debut among members of the population. Targeting 

high-risk groups is not possible. Modeling shows greater impact with a routine rather than a risk-based 

strategy. The target age of 11-12 years will allow vaccination of most females before sexual debut. 

Delivery of a three-dose series will be challenging in this age group, but the implementation advantages 

include the opportunity provided by the young adolescent healthcare visit recommended by a variety of 

professional organizations, when other vaccines are provided. 

Data from bridging immunogenicity studies show high antibody titers after vaccination in this age group. 

The duration of protection is not known at this time, but five-year data do not show evidence of waning 

immunity. Studies will be conducted on an ongoing basis to monitor duration. A 2005 published study of 

2002 NSFG data showed that 26% of females had vaginal sex by 15 years of age and 77% by 19 years 

of age (Mosher, et al.). A 2003 published study showed that 40% of females had acquired HPV infection 

by two years after sexual debut and >50% had acquired infection by four years after sexual debut (Winer, 

et al.). 

Recommendation 2 is for catch-up vaccination. “ACIP recommends vaccination for females 13-26 years 

of age who have not been previously vaccinated. Ideally, vaccine should be administered before onset of 

sexual activity, but females who are sexually active should still be vaccinated.” The workgroup’s rationale 

and data to support catch-up vaccination are outlined below. 

ACIP Meeting Minutes June 29-30, 2006 Page 16 

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ACIP Meeting Minutes June 29-30, 2006 Page 17 

Females 13-26 years of age who are not yet sexually active can be expected to fully benefit from 

vaccination due to non-exposure to HPV vaccine types. Sexually active females in this age group may 

not fully benefit from the vaccine due to pre-existing infection with HPV vaccine types. However, only a 

small percentage of females are likely to have been infected with all four HPV vaccine types. The 

vaccine would provide protection against disease caused by other HPV vaccine types for women already 

infected with >one HPV vaccine types. The overall effectiveness of the vaccine would be lower in a 

population of sexually active women, but most females will still derive benefit from vaccination. 

The benefit of vaccination will decrease with increasing age because more females will have been 

infected with HPV vaccine types. Minimal data have been generated on the cumulative incidence of HPV 

infection by specific type. Serologic studies underestimate cumulative incidence for HPV because not all 

persons with HPV develop an antibody response after natural infection. Some studies show that ~60% of 

females with HPV 16 develop antibody. Detection of HPV DNA underestimates cumulative incidence 

because only a point prevalence estimate is provided and most infections clear within one year. 

Unpublished data from Merck’s quadrivalent HPV vaccine trials showed that >90% of North American 

subjects were sexually active at the time of enrollment. PCR or serology results showed that 24.4% of 

women 16-26 years of age had evidence of past or present infection with at least one HPV vaccine type; 

76% were naïve to all types based on methods used in the study; and <1% had evidence of infection with 

all four types. These data also showed that the percentage of women with evidence of past or present 

infection increased with increasing age. Of this cohort, 14% had evidence of infection with HPV 16/18 at 

16 years of age and 24% had evidence of infection at >23 years of age. 

Data from CDC’s 1991-1994 National Health and Nutrition Examination Survey (NHANES) were also 

reviewed to ensure the sample was representative of the general U.S. non-institutionalized population. 

Seroprevalence of HPV 16 was 6.8% in females 12-19 years of age and 24.7% in females 20-29 years of 

age. These data underestimate cumulative incidence and estimates were made based on some 

assumptions. The cumulative HPV 16 infection by 20-29 years of age would be ~41% with the 

assumption that only 60% of women develop antibody after natural infection. Even with assumptions for 

underestimates, the majority of women 20-29 years of age would still benefit from a vaccine that 

protected against HPV 16. 

The workgroup proposes to include the following statement about cervical cancer screening in the 

ACIPRecommendation. “There is no change in the recommendations for cervical cancer screening. 

Vaccinated females could be subsequently infected with non-HPV vaccine types. Sexually active females 

could have been infected prior to vaccination. The decision to vaccinate should not be based on Pap 

testing, HPV DNA testing or HPV serologic testing.” 

The workgroup proposes the following language for simultaneous administration of the quadrivalent HPV 

vaccine. “The quadrivalent HPV vaccine can be administered with other age-appropriate vaccinations, 

such as Tdap, MCV4 or HepB vaccine. The immune response to both HepB and quadrivalent HPV 

vaccines is not inferior when administered at the same or a different visit. No data have been produced 

for co-administration with Tdap or MCV4, but the quadrivalent HPV vaccine is not a live vaccine. No 

components have been found to adversely impact safety or efficacy of other vaccinations.” The proposed 

language is consistent with ACIP’s general recommendations for other non-live vaccines. 

The workgroup considered the implications of the routine and catch-up recommendations on price and 

supply. Merck’s private-sector price of the vaccine is $120/dose or $360/series. The workgroup 

calculated the potential doses that would be needed in the first year based on the broad proposed 

recommendations. Based on an optimistic uptake of 20% and full administration of all three doses, 2.4 

million doses would be needed for females 11-12 years of age and 19.2 million doses would be needed 

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for females 11-26 years of age. Merck has given assurances that its vaccine supply is adequate to meet 

these estimates in the first year. 

Recommendation 3 is for five special situations. The quadrivalent HPV vaccine can be administered in all 

of these situations. One: females with “an equivocal or abnormal Pap test. However, providers should 

advise patients of the potential to already have been infected with an HPV vaccine type. Data do not 

indicate that the vaccine will have any therapeutic effect on existing cervical lesions or HPV infection.” 

The workgroup’s rationale and data to support special situation 1 are outlined below. 

Infection with any of the 40 high- or low-risk genital HPV types is possible. The likelihood of infection with 

HPV 16/18 increases with the severity of Pap test results. Infection with all four types would be unlikely. 

The patient may not be infected with any vaccine type. Vaccination would provide protection against 

infection with HPV vaccine types not already acquired. Data from CDC’s HPV Sentinel Surveillance 

Project (SSP) show that most women with an abnormal Pap test have no evidence of HPV 16/18 

infection. 

Two: females with “a positive HPV tests using the Digene Hybrid Capture II®

 (HCII) assay. However, 

providers should advise patients of the potential to already have been infected with an HPV vaccine type. 

Data do not indicate that the vaccine will have any therapeutic effect on existing cervical lesions or HPV 

infection.” The workgroup’s rationale and data to support special situation 2 are outlined below. 

FDA approved the use of the HCII test for women <30 years of age with atypical squamous cells of 

undetermined significance (ASC-US) on Pap tests. A positive test indicates infection with any of 13 highrisk types, but the test does not identify specific HPV types. Testing for specific types is not currently 

available in routine clinical practice. Vaccination would provide protection against infection with HPV 

vaccine types not already acquired. Unpublished data from CDC’s HPV SSP showed that among 118 

females 14-26 years of age with positive DHCII results, 37% were positive for HPV 16/18. 

Three, females with “genital warts or a history of genital warts. However, data do not indicate the vaccine 

will have any therapeutic effect on existing genital warts or HPV infection.” The workgroup’s rationale to 

support special situation 3 is outlined as follows. A history or clinical examination of genital warts 

indicates HPV infection, primarily with HPV 6/11. Individuals may not have had infection with both HPV 

6/11 or 16/18. Vaccination in this situation would provide protection against the vaccine HPV types not 

already acquired. Four, “immunosuppressed patients. Immune response and vaccine efficacy may be 

less than in immunocompetent persons.” Five, “lactating women.” 

Recommendation 4 is for precautions and contraindications. “Vaccination should be deferred until after 

moderate or severe acute illnesses improve. A history of hypersensitivity or severe allergic reaction to 

yeast or any other vaccine component should be classified as a contraindication. Initiation of the vaccine 

series should be delayed until after completion of the pregnancy. Completion of the vaccine series 

should be delayed until after the pregnancy if a pregnancy is identified after initiating the vaccine series. 

There is no indication for intervention if a vaccine dose has been administered during pregnancy. Cases 

of vaccination during pregnancy should be reported to the registry. FDA gave the quadrivalent HPV 

vaccine a category B designation. The quadrivalent HPV vaccine has not been causally associated with 

adverse outcomes of pregnancy or adverse events to the developing fetus. More safety data are needed 

on vaccination in pregnancy.” 

ACIP Vote on the HPV Vaccine 

ACIP Meeting Minutes June 29-30, 2006 Page 18 

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ACIP Meeting Minutes June 29-30, 2006 Page 19 

Recommendation 1. ACIP made several suggestions to strengthen the proposed recommendation on 

routine vaccination. 

• Add language to emphasize the adolescent platform and the rationale of targeting the 

recommendation to females 11-12 years of age. 

• Add language to explicitly state that ACIP’s intention is for health plans to cover 

administration of the vaccine in females as young as 9 years of age. 

• Add language to clearly delineate the minimum interval between the three doses. 

Drs. Markowitz and Barr provided additional details on the proposed recommendation for routine 

vaccination. 

• “Naïve” means an individual had no antibody with PCR testing based on measurements 

that have been used to date. However, whether an individual is truly naïve cannot be 

fully determined because some persons do not develop antibody. 

• Data from Merck’s clinical trial of ~1,200 subjects who were seropositive and PCRnegative at baseline showed that women who were infected and cleared the infection 

were partially rather than fully protected. Administration of the vaccine in this population 

was 100% effective in preventing recurrent disease, but event rates were low. 

• Merck has given assurances that the vaccine can be readily supplied across all the 

proposed recommended age cohorts. 

Dr. Abramson called for a motion on the proposed recommendation for routine vaccination. Dr. Gilsdorf 

moved as follows: “ACIP recommends routine vaccination of females 11-12 years of age with three 

doses of quadrivalent HPV vaccine. The vaccine series can be initiated in females as young as 9 years 

of age at the discretion of the provider.” Ms. Stinchfield seconded the motion and Dr. Abramson 

proposed a friendly amendment for the recommendation to emphasize the adolescent platform. 

The motion passed by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Recommendation 2. Dr. Allos pointed out that ACIP previously voted to make the HepB vaccine 

recommendation risk-based rather than age-based. For internal consistency with the HPV 

recommendation, she strongly urged ACIP to revisit the HepB vaccine language and include an agebased recommendation for adults. Dr. Abramson confirmed that the Hepatitis B Workgroup has already 

been charged to address this issue. 

Drs. James Turner and Stanley Gall, the ACIP liaisons for the American College Health Association 

(ACHA) and American College of Obstetricians and Gynecologists, respectively, expressed strong 

support for the proposed recommendation on catch-up vaccination. 

Dr. Abramson called for a motion on the proposed recommendation for catch-up vaccination. Dr. Gilsdorf 

moved as follows: “ACIP recommends vaccination for females 13-26 years of age who have not been 

previously vaccinated. Ideally, vaccine should be administered before onset of sexual activity, but 

females who are sexually active should still be vaccinated.” The motion was seconded by Dr. Womeodu 

and passed by a majority vote. The disposition of the vote is as follows: 

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ACIP Meeting Minutes June 29-30, 2006 Page 20 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Recommendation 3. Dr. Abramson called for a motion on the proposed recommendation for special 

situations. Dr. Gilsdorf moved as follows: “ACIP accepts the proposed recommendations for the five 

special situations of an equivocal or abnormal Pap test, positive HPV test, genital warts, 

immunosuppression, and lactating women.” The motion was seconded by Ms. Stinchfield and passed by 

a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Recommendation 4. Dr. Markowitz provided clarification on the proposed recommendation for 

precautions and contraindications. The workgroup proposes to classify moderate or severe acute illness 

as a precaution; hypersensitivity as a contraindication; and pregnancy as a contraindication. 

ACIP made several suggestions to strengthen the proposed recommendation. 

• Make the pregnancy recommendation a precaution rather than a contraindication to avoid 

the need to include language on pregnancy tests and similar issues. 

• Include the pregnancy recommendation in a separate “vaccination in pregnancy” section 

or under “special circumstances” rather than in the precautions and contraindications 

section. 

• Include an explicit statement that pregnancy testing before vaccination is not necessary. 

• Replicate language on pregnancy from ACIP’s previous statements. For example, advise 

providers to ask patients about their pregnancy status, record the response in the chart 

and proceed with immunization. 

• Change “hypersensitivity” to “immediate hypersensitivity.” 

• Do not include a statement about pregnancy testing because this language will 

complicate the recommendation. 

• Add “should not be based on pregnancy testing” to the pregnancy language that states 

“the decision to vaccinate should not be based on screening.” 

Dr. Abramson acknowledged that ACIP would continue to be challenged in addressing the use of 

vaccines in pregnancy. As a result, he announced the ACIP’s intention to form a new Vaccines in 

Pregnancy Workgroup to address questions related to administration of vaccines during pregnancy. In 

the interim, however, he called for a motion on the proposed recommendation for precautions and 

indications. 

Dr. Gilsdorf moved as follows: “ACIP recommends deferring vaccination in females with moderate or 

severe acute illnesses until after the illness improves. ACIP recommends classifying a history of 

hypersensitivity or severe allergic reaction to yeast or any vaccine component as a contraindication. 

ACIP recommends moving pregnancy to the special situations section and adding new language to the 

screening section to clarify that vaccination should not be based on pregnancy testing.” Dr. Womeodu 

seconded the motion. 

Drs. Abramson and Campbell proposed two friendly amendments to the motion. “Hypersensitivity” should 

be changed to “immediate hypersensitivity.” The following language should be moved with the revised 

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pregnancy statement to the special situations section. “Initiation of the vaccine series should be delayed 

until after completion of the pregnancy. Completion of the vaccine series should be delayed until after the 

pregnancy if a pregnancy is identified after initiating the vaccine series. No indication for intervention has 

been established if a vaccine dose has been administered during pregnancy. Cases of vaccine in 

pregnancy should be reported to the registry. FDA gave the quadrivalent HPV vaccine a category B 

designation during pregnancy. The quadrivalent HPV vaccine has not been causally associated with 

adverse outcomes of pregnancy or adverse events to the developing fetus. More safety data are needed 

on vaccination in pregnancy.” 

The motion passed by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Proposed VFC Resolution 

Dr. Angela Calugar, of CDC, proposed the following language to add the quadrivalent HPV vaccine to the 

VFC Program. ACIP’s VFC resolution on February 1, 2006 would be updated with “add HPV vaccines.” 

“HPV” would be added to the existing list of 15 diseases covered by vaccines in the VFC Program and 

would be administered as described in other VFC resolutions. 

Eligible groups include females 9-18 years of age. A three-dose series for the quadrivalent HPV vaccine 

is recommended for females 11-12 years of age with the following schedule: dose one at an elected 

date; dose two at 2 months after dose one; and dose three at 6 months after dose one. The minimum 

age of vaccination is 9 years. The minimum interval from dose one to two is 4 weeks. The minimum 

interval from dose two to three should not be less than 12 weeks. Catch-up vaccination is recommended 

for females 13-18 years of age who have not been previously vaccinated or have not completed the full 

series. Eligible females as young as 9 years of age can be vaccinated. 

Proposed statements for an interrupted vaccine schedule, recommended dosage, and special situations 

for immunocompromised persons and lactating women are in coordination with ACIP’s HPV 

recommendations. Based on ACIP’s previous vote, pregnancy will be included under special situations. 

In the precautions and contraindications section, acute illnesses will remain; vaccination during 

pregnancy will be deleted; and hypersensitivity or allergy to vaccine components will remain and be 

changed to “immediate hypersensitivity.” 

ACIP Vote on the Proposed VFC Resolution 

Mr. Beck expressed concern about the ability to achieve the projected levels of vaccine delivery, 

particularly with application of an estimated 70% coverage rate among adolescents. These estimates will 

tremendously impact and may substantially increase cost-effectiveness. Mr. Beck acknowledged ACIP’s 

responsibility to be prudent in its VFC resolution. Most notably, a statement should be made for the 

record if ACIP’s position is that the estimates are not realistic. This type of language could encourage 

financial analysts to obtain more reliable data. 

ACIP Meeting Minutes June 29-30, 2006 Page 21 

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Drs. Abramson and Pickering responded to Mr. Beck’s concerns. Issues related to vaccine financing are 

beyond the scope of ACIP’s charter. However, NVAC recently announced its new role of addressing 

financing for HPV and all other vaccines. Moreover, VFC is an entitlement program of vaccine coverage 

to eligible children through 18 years of age. Issues related to vaccine cost-effectiveness and financing 

are outside of the VFC Program. 

Drs. Lieu and Finger also made comments on the cost-effectiveness of the HPV vaccine. CDC’s data 

clearly demonstrate that the vaccine is a solid investment regardless of the specific coverage rate 

achieved. The data also showed an acceptable range for cost-effectiveness in both the catch-up and 

vaccination-only strategies. The base case scenario assumed a vaccination-only strategy of females 12 

years of age, a 50-year time horizon, and no herd immunity. However, the data clearly demonstrated that 

cost-effectiveness would be improved with a higher coverage rate. 

Dr. Mark Feinberg, of the Merck Vaccine Division, expressed Merck’s strong interest in monitoring the 

utilization rates of the HPV vaccine over time and documenting the value of this investment to the 

healthcare community. Merck has established a program to provide the vaccine free of charge to clinics 

and private physicians’ offices; eligibility criteria include ineligibility for the VFC program, low 

socioeconomic status, appropriate age range (19 years and above), uninsured and <200% of the federal 

poverty limit. Merck’s program will be available for HPV and all of its other vaccines. Dr. Feinberg 

emphasized that the strength of ACIP’s recommendations will play an important role in reaching high 

immunization coverage levels. 

Ms. Linda Murphy, the ACIP ex- officio representative for the Centers for Medicare and Medicaid Services 

(CMS), clarified that Medicaid recipients who initiate the HPV vaccine series under the VFC Program at 

18 years of age can complete the series after 18 years of age under Medicaid. This option is not 

available under the VFC program because the legislation specifically covers vaccines in children up to 18 

years of age only. 

Drs. Poland and Campos-Outcalt suggested two changes to the proposed resolution. “HPV vaccine” 

should be changed to “quadrivalent HPV vaccine.” Eligible groups should be changed to females 9 

“through” 18 years of age rather than “to.” 

Dr. Abramson called for a motion on the proposed VFC resolution. Dr. Gilsdorf moved as follows: “ACIP 

approves the VFC resolution for the HPV vaccine.” The motion was seconded by Dr. Morse and passed 

by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

The participants applauded the outstanding leadership of Drs. Gilsdorf and Markowitz in guiding the HPV 

Vaccine Workgroup in developing recommendations for an extremely complex vaccine. 

VARICELLA VACCINE 

The series of presentations and ACIP’s discussion and vote on the varicella vaccine are set forth below. 

ACIP Meeting Minutes June 29-30, 2006 Page 22 

Update on Varicella Epidemiology 

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ACIP Meeting Minutes June 29-30, 2006 Page 23 

Dr. Dalya Guris, of CDC, reported data on varicella vaccination coverage in the United States, disease 

trends and outbreaks, the accumulation of susceptible persons, and one and two doses of varicella 

vaccine. National Immunization Survey (NIS) data show that the varicella vaccination program (VVP) has 

resulted in a steady increase in vaccination coverage from 1997-2004. Coverage among children 19-35 

months of age was 88% in 2004. Vaccination coverage ranged from 70%-94% among states. The 

District of Columbia and 45 states have implemented childcare or school entry requirements. 

Two studies published in 2005 demonstrated that the VVP has also resulted in a substantial reduction in 

morbidity and mortality (Zhou and Nguyen, respectively). Hospitalizations decreased by 88% and 

ambulatory visits decreased by 59% in 2002 compared to 1994-1995. Hospitalizations due to varicella 

decreased in all age groups with the largest reduction among children <10 years of age. The average 

number of varicella deaths in 1999-2001 compared to 1990-1994 decreased in all age groups with a 92% 

reduction among children 1-4 years of age. 

Data from two of CDC’s Varicella Active Surveillance Project (VASP) sites showed that varicella cases 

quickly decreased in the early years of the program due to a rapid increase in vaccination coverage. 

However, a plateau has been observed in the number of varicella cases at the VASP sites over the past 

few years despite high vaccination coverage. 

A similar trend was seen in Texas in which varicella vaccination coverage reached 85% in 2004, but the 

decreasing trend in the number of cases did not persist. Provisional surveillance data reported by Texas 

in 2005 showed that most varicella cases were among children 5-9 years of age. The number of cases 

among children 10-14 years of age has steadily increased over the past four years. In 2005, the 

vaccination status was known for ~70% of the reported cases; 82% of children 1-4 years of age and 92% 

of children 5-9 years of age were vaccinated. 

Varicella in vaccinated persons is less severe compared to disease among unvaccinated persons. VASP 

data from 2002-2004 showed that ~30% of vaccinated cases had >250 lesions compared to ~65% of 

unvaccinated cases. Although hospitalizations and deaths rarely occur among vaccinated varicella 

cases, breakthrough disease is infectious and poses a risk for persons at risk for severe disease. An 

adult death was reported in Florida in 2005 following exposure to chickenpox from his vaccinated child. 

Several varicella outbreaks have been reported among highly vaccinated schoolchildren with coverage 

ranging from 96%-100% and overall attack rates ranging from 11%-17%. Attack rates were up to 41% in 

some classrooms. These outcomes demonstrate that a one-dose vaccination policy does not provide 

sufficient herd immunity levels to prevent school outbreaks. Moreover, the accumulation of susceptible 

persons may result in larger epidemics in the future because children are entering into adolescence and 

adulthood without exposure to varicella. A shift of cases toward older ages has already been observed at 

one VASP site. The peak age of cases was 3-6 years in 1995 compared to 9-11 years in 2004. 

The risk of exposure to varicella-zoster virus (VZV) decreases as the overall disease incidence declines. 

In a population with 100% coverage, 20% of persons will remain susceptible because vaccine 

effectiveness is ~80%. Both vaccinated and unvaccinated susceptible persons are accumulating and will 

be at risk for disease and outbreaks later in life when disease can be severe. CDC calculated the 

accumulation of susceptible persons with a one-dose vaccination program based on the following 

assumptions: a 4 million birth cohort, 95% coverage rate, 80% vaccine effectiveness, and 30% of 

vaccinated persons susceptible to typical disease. The findings showed that ~40% of susceptible 

persons would have the potential to develop typical disease with >250 or more lesions if exposed to VZV. 

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Most field studies indicate that one dose of varicella vaccine is 80%-85% effective. Several risk factors 

for vaccine failure were assessed, including time since and age at vaccination, asthma, use of steroids, 

eczema, and cold chain problems. However, the literature is not consistent on identifying risk factors for 

vaccine failure. A recent ten-year prospective study showed that the cumulative rate of breakthrough 

disease after one dose increased throughout the follow-up period. The rate did not increase after year 6 

among children in the two-dose group. 

No additional cases were observed among children in the two-dose group during the remainder of the 

follow-up period, but breakthrough disease continued to occur among children in the one-dose group 

(Kuter, et al.). The study used historical population incidence rates to compare the efficacy of two versus 

one dose. The estimated two-dose vaccine efficacy of 98.3% was significantly higher than the estimated 

one-dose vaccine efficacy of 94.4%. The attack rate among children in the one-dose group was 3.3-fold 

higher than the attack rate among children in the two-dose group. 

Overall, the VVP has resulted in substantial disease reduction in the first ten years, but challenges still 

exist. One-dose vaccination is 80%-85% effective. Breakthrough cases are infectious and disease 

among vaccinated children can be severe. Outbreaks continue to occur even among highly vaccinated 

schoolchildren and their investigations are placing an increasing demand on state and local health 

departments and school staff. 

Varicella incidence is not continuing to decline. The age of varicella cases is shifting to adolescents. 

Persons susceptible to varicella are accumulating due to reduced incidence. Adults will be at higher risk 

for disease at times when disease can be severe, such as infection during pregnancy. The potential 

exists for large outbreaks in high schools and colleges. One-dose vaccination will not provide adequate 

protection. 

Immune Responses to One and Two Doses of Varicella Vaccine 

Dr. Anne Gershon, of Columbia University (CU), serves as a consultant to the Varicella Workgroup. She 

presented data to support the workgroup’s proposed recommendation for a routine two-dose regimen of 

varicella vaccine to children. The VVP should reduce the varicella burden in childhood, but if 

breakthrough disease develops, there is potential transmission of wild type VZV, potential for 

development of latent infection, and possible zoster. The VVP should also prevent accumulation of fully 

or partially susceptible young adults who would be at risk for developing severe chickenpox. However, 

primary immune failure of even 5% after a single dose could result in 200,000 non-immune children 

annually. 

A 1991 published study on seroconversion among 2,442 children after one dose of VARIVAX suggested 

that primary immune failure was unusual (4%) (White, et al.). The study methods included a gp ELISA 

test, a cutoff for immunity of >3 units, and a low GMT of 1:12. It was projected that children with no 

detectable antibodies might have cell-mediated immunity (CMI) against VZV and children with >5 units by 

gp ELISA six weeks post-vaccination were less likely to develop breakthrough infections over time than 

those with lower titers six weeks post-vaccination. 

New unpublished data suggest that primary vaccine failure may be more common after one dose than 

previously reported in the literature (Michalik, et al.). The following methods were used in this study. A 

cohort of 80 healthy susceptible children with a mean age of 16 months was given one dose of VARIVAX. 

Sera were obtained from the cohort both before and 16 weeks after vaccination. The fluorescent 

antibody to membrane antigen (FAMA) test was used to measure seroconversion rates. The FAMA test 

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ACIP Meeting Minutes June 29-30, 2006 Page 25 

has been validated and published in the literature. The percentage of children who achieved a titer >1:4 

was 76%. In this study, the primary vaccine failure rate was 23%. 

Other recent unpublished data also show a high primary vaccine failure rate using similar methods 

(LaRussa, et al.). A cohort of 56 healthy susceptible children with a mean age of 25 months was given 

one dose of VARIVAX. Sera were obtained from the cohort both before and six weeks after vaccination. 

The FAMA test was used to measure seroconversion rates. The percentage of children who achieved a 

titer >1:4 was 88%. In this study, the primary vaccine failure rate was 12%. 

Unpublished data from a ten-year study at a VASP site over the 1995-2004 time period suggest that the 

incidence of breakthrough varicella may be increasing (Chaves, et al.). A substantial decrease was seen 

in circulation of wild type VZV, but a slow increase in the breakthrough rate was observed up until year 9. 

Although these results should be validated in other settings, the data demonstrate an accumulation of 

children with primary vaccine failure and an inadequate initial response that falls below the threshold for 

protection. 

Four studies published in 2002 and 2004 demonstrated an increase in breakthrough varicella over time 

that suggests some degree of waning immunity (Galil, Lee, Tugwell, Vazquez). More breakthrough cases 

of varicella were observed in children vaccinated 3-5 years previously than in those vaccinated within a 

shorter interval. However, these data are confounded by different ages and forces of infection. 

 

Data from CU revealed that a two-dose regimen of varicella vaccine would provide a boost of immunity. 

These calculations support the immunologic concept of the importance of an initial burst of the host 

response to establish long-term anti-viral immunity. CU’s calculations are also consistent with an actual 

case of a physician who was immunized in experimental studies in 1979 and never developed chickenpox 

or zoster despite exposure to chickenpox in an emergency room and from his two children. 

Unpublished data showed an increase in gp ELISA titers in children who received two doses of varicella 

vaccine (Levin). The data showed that the seroconversion rate of 87.3% six weeks after dose one 

increased to 99.5% following dose 2. The GMT also dramatically increased from 12.8 after dose 1 to 

141.5 following dose 2. Other unpublished data also showed a marked increase after two doses of 

measles, mumps, rubella and varicella (MMRV) (Kuter). Seroconversion rates and GMTs to VZV 

increased from 87% and 12, respectively, after dose 1 to 99% and 478, respectively, following dose two. 

Laboratory data showed that two doses of varicella vaccine can increase CMI in children and provide a 

significant boost for at least one year (Arvin). The mean CMI in the one-dose group of 39 children was 

9.3 at 1 year post-vaccination compared to 22.2 in the two-dose group of 39 children. A 1995 published 

study showed that a second dose of varicella vaccine can provide an effective boost in immunity 6 years 

following primary vaccination (Watson). During the time period before and 3 months after the booster, the 

mean GMT increased from 25.7 to 119 and CMI increased from 40.3 to 61.4. 

A 2004 published study showed that the efficacy of two doses of varicella vaccine over 10 years was 

greater than one dose (Kuter, et al.). Varicella was 3.3-fold lower in children after two doses than after 

one dose. Breakthrough disease was significantly decreased in children who received two doses. The 

10-year efficacy of 94.3% after dose one versus 98.3% after dose two was significant. The modified 

severity of varicella even with one dose suggests evidence of priming of the immune response in some 

children. 

The Varicella Workgroup reached the following conclusions based on its review of the literature. 

Available evidence suggests that two doses of varicella vaccine are superior to one. Dramatic boosts in 

humoral and cellular immunity and better protection against disease were seen after two doses. 

Breakthrough varicella is probably due mostly to partial or incomplete primary vaccine failure after one 

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dose rather than waning immunity. The evidence suggests that primary priming of the immune response 

occurs in many vaccinees after one dose, but the initial burst is insufficient for protection after normal 

decline. 

The single dose regimen was expected to require reassessment after successful introduction of routine 

varicella vaccination. Introduction of MMRV provides a solid opportunity to introduce a two-dose regimen. 

A shift in varicella disease burden to young adults can be predicted without a change to a two-dose 

regimen. This trend would be based on an accumulation of young adults with complete or partial primary 

vaccine failure; an inadequate initial immune response that declines to below protective levels; and a 

reduction of opportunities for boosting from varicella exposures. Outbreak control is problematic, 

expensive and will not prevent the shift of infection to young adults. 

Projected Benefits and Costs of a Second Dose of Varicella Vaccine 

Dr. Tracy Lieu is a member of the Varicella Workgroup. She presented data prepared and analyzed by 

Dr. Fangjun Zhou, of CDC, on the projected benefits and costs of a second dose of varicella vaccine. As 

presented in 2005, the ~$1 million cost per life-year saved appeared to be high and the cost of MMRV 

was unknown. In 2006, outbreak costs have been studied and the previous data analysis has been 

updated to credit the vaccine with preventing varicella morbidity. 

The data analysis was based on several assumptions. Varicella incidence rates were obtained from 

VASP. A second dose of vaccine would reduce varicella by 79%. Immunity would be life-long from the 

second dose. An outbreak costs $5,900. The benefits of the vaccine in preventing Group A 

Streptococcus and averting zoster were not included. The data analysis showed the following results 

based on these assumptions. 

Incremental annual health benefits for the U.S. population using MMRV vaccine for the second dose 

would include the prevention of 400,000 varicella cases (10% of potential cases) and the saving of five 

lives. The cost of varicella vaccine (using MMRV vaccine) is $58 per child for one dose and $116 per 

child for two doses. Assuming that 63% of the MMRV vaccine would be given in the public sector, the 

incremental national cost would be $218 million; savings from varicella prevented would be $124 million; 

and the net incremental cost would be $93 million. The net costs (savings) would be $967 million with the 

one-dose program compared to $874 million with the two-dose program. The two-dose program would 

also be cost-saving compared with no intervention. 

The second dose of varicella vaccine would save few lives, but the vaccine should be credited for 

preventing disease cases in addition to deaths. Two studies published in 1998 and 2003 that interviewed 

parents and older persons about the value in preventing varicella and zoster were used to estimate 

QALYs saved (Bala and Brisson, respectively). Using these estimates, the workgroup’s analysis showed 

that the second dose saved an additional 1,365 QALYs and resulted in an incremental $96,000 cost per 

QALY saved from a societal perspective. 

The data analysis included a comparison to other vaccines. The Zhou data showed that the second dose 

of varicella vaccine would prevent 400,000 disease cases; save 1,400 QALYs; cost $311 million for the 

direct cost of vaccination and net societal cost; and result in $96,000 per QALY saved. The Lee data 

showed that pertussis vaccination of adolescents would prevent 31,000 disease cases; save 1,600 

QALYs; cost $77 million for the direct cost of vaccination and net societal cost; and result in $20,000 per 

QALY saved. The Shepard data showed that meningococcal vaccination would prevent 270 disease 

cases; save 1,800 QALYs; cost $432 million for the direct cost of vaccination and net societal cost; and 

result in $138,000 per QALY saved. 

ACIP Meeting Minutes June 29-30, 2006 Page 26 

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Secondary analyses to credit MMRV with preventing related conditions would improve the base case 

cost-effectiveness. Savings from averting Group A Streptococcus would add an incremental cost per 

QALY saved of $91,000. Benefits from preventing zoster would add an incremental cost per QALY saved 

of $17,000. However, uncertainties must also be considered in decisions to add a second dose of 

varicella vaccine. The duration of immunity after the second dose is unknown. Catch-up vaccination and 

its cost-effectiveness have not been analyzed to date. 

Overall, the data analysis showed that the cost-effectiveness of a second dose of varicella vaccine is 

likely to fall in the reasonable range. Important factors along with cost-effectiveness should be weighed, 

such as the social disruption from school outbreaks and burden to public health agencies. 

State Health Department Perspective on Varicella Outbreak Response 

Dr. Dale Morse is a member of the Varicella Workgroup. He presented a state health department’s 

perspective on a two-dose varicella vaccination schedule. The failure of the one-dose measles 

vaccination program should be reviewed to avoid making the same mistakes with varicella. Measles 

cases and outbreaks continued to occur in the United States despite the one-dose measles elimination 

program to end indigenous measles in October 1982. New York had a 99% reduction in measles cases, 

but cases and outbreaks continued to occur in high schools. 

In the late 1980s, New York and other states began to actively exclude any child from school entry 

without a history of measles immunization. States continued to control outbreaks and monitor rates while 

the debate continued over the need for a second dose of measles vaccine. New York adopted a state 

policy of two-dose measles vaccine following outbreaks in college settings. In a four-month period, 21 

outbreaks occurred and 90% of college students were immunized for measles. New York’s administration 

of >50,000 doses cost >$850,000 for the vaccine and ~$3 million for outbreak control. ACIP soon 

developed a national policy of two-dose measles vaccine following the New York State policy. 

CDC administered a survey in 2004 to 57 state immunization grantees to determine the extent of varicella 

outbreaks in the United States. Of 93% of states that responded to the survey, 85% reported being 

contacted about varicella cases or outbreaks; 15% estimated being contacted for 75%-100% of local 

outbreaks; and 87% responded to outbreaks at the state or local level. CDC used a standard tool to 

collect information and learned that seven grantees reported “personnel” as the majority of costs for 

outbreak investigations. The grantees also reported that a typical response to a school outbreak cost 

$3,000. An active outbreak response in which an immunization clinic was established cost $6,000. A 

hospital outbreak investigation cost $7,700. 

Of CDC’s immunization grantees, Connecticut has maintained more active surveillance of varicella cases 

and outbreaks than other states in its population of ~3.5 million persons. Of 1,038 cases detected in 

schools from September 2003-June 2004, 44% were outbreak-related. Of 41 outbreaks that occurred in 

41 schools, 93% were in elementary schools. The mean age of cases was nine years. The duration of 

outbreaks in the schools among well immunized children ranged from 15-93 days. 

ACIP responded to these outbreaks in June 2005 by recommending a second dose of varicella vaccine 

during an outbreak for persons who had received one dose, if resources permitted. Several states have 

attempted to comply with the ACIP guidance. For example, an outbreak continued over ~3 months in a 

Maine elementary school with ~350 students despite an immunization rate of 98% with one dose. An 

immunization campaign ultimately ended the outbreak. 

ACIP Meeting Minutes June 29-30, 2006 Page 27 

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Maine identified several challenges in responding to the outbreak of October 2005-January 2006. A 

tremendous burden of 382 extra hours was placed on school and health personnel. School and work 

days were missed and the outbreak response cost $26,761. Recognition of the outbreak was delayed. 

Public and private providers were reluctant to accept an immunization clinic and exclude non-vaccinated 

children. Difficulties were encountered with the clinical case definition and confirmatory laboratory tests. 

State law currently requires one dose of varicella vaccine and does not cover school exclusion. The 

second dose of the vaccine was not covered by insurers. 

Similar to the one-dose measles vaccine program, the one-dose varicella vaccination policy is failing to 

eliminate a childhood disease. The outbreak control policy is not effective in controlling varicella 

outbreaks. Susceptible persons are accumulating and will be at risk later in life when disease can be 

more severe. Efforts are underway by professional organizations to address these concerns. 

The American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID) voted to 

recommend universal administration of a second dose of varicella-containing vaccine. The Council of 

State and Territorial Epidemiologists (CSTE) adopted a position statement during its June 2006 meeting 

recommending that ACIP consider a universal two-dose varicella vaccination policy with catch-up 

provisions. CSTE adopted the position statement due to the endemic occurrence of varicella cases, 

outbreaks among well-immunized children who received a single dose of varicella vaccine, and the 

demonstrated futility of outbreak follow-up and control measures. 

Dr. Jane Seward, of CDC, and Dr. Barbara Kuter, of Merck, provided additional details related to the 

proposed catch-up strategy for varicella vaccination. The age limit for catch-up vaccination could 

potentially range from children 6-12 years of age to adults 22 years of age who were 12 years of age in 

1995 and received one dose. Merck’s studies show that the second dose of vaccine will provide a solid 

boost regardless of the level of antibody or time since the first dose. 

Consideration of a Universal Two-Dose Recommendation for Varicella Immunization 

Dr. Judith Campbell, the Varicella Workgroup Chair, covered several topics to facilitate ACIP’s discussion 

and vote on a routine two-dose policy for varicella vaccination. The workgroup is soliciting ACIP’s vote in 

two areas. Recommendation 1 proposes a change in the current varicella vaccination policy. Children 

would be routinely vaccinated with two doses at 12-15 months of age for dose one and 4-6 years of age 

for dose two with a caveat regarding the minimum interval between the two doses. 

Recommendation 2 proposes catch-up vaccination for children, adolescents and young adults who 

previously received one dose, to improve individual protection against varicella and for more rapid impact 

on school outbreaks. Catch-up vaccination could be implemented during routine healthcare visits and 

through school and college entry requirements. 

The workgroup extensively reviewed the varicella immunization science in formulating the 

recommendations. Initial implementation of the varicella immunization policy in 1995 has resulted in 

successful reductions in varicella incidence, morbidity and mortality. However, the reduction in varicella 

incidence has reached a plateau over the past 4-5 years in states with high immunization coverage rates. 

Although high immunization rates have been achieved in active surveillance sites and many states, 

breakthrough infections and outbreaks in school settings continue to occur. Breakthrough infections are 

contagious and frequently serve as the source of outbreaks or ongoing transmission to persons who are 

susceptible or at high risk for severe disease. 

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Varicella vaccine effectiveness was estimated at 80%-85% post-licensure. Of all varicella vaccine 

recipients, 15%-20% are non-responders or partial responders after one dose. The incidence of 

breakthrough infection in children who received one dose has increased with time since vaccination. The 

susceptible population is accumulating due to the decreased overall incidence of wild type varicella. The 

higher risk for more serious disease among adolescents and adults will pose a risk for large outbreaks in 

high schools and colleges. 

Two doses of varicella vaccine parallel the immune response to natural infection with higher antibodies 

levels measured by FAMA or gp ELISA and cellular immune response measured by stimulation index. 

The number of breakthrough infections is significantly lower in two-dose recipients compared to one-dose 

recipients. The workgroup acknowledges that the varicella immunization science is limited because the 

duration of two doses is not known beyond 10 years. 

The workgroup discussed and considered the varicella immunization standard of care from diverse 

sources in formulating the recommendations. Surveys administered to providers show that most 

pediatricians and family practitioners have experience with breakthrough infections and will give a second 

dose of varicella vaccine if recommended by ACIP. The availability of MMRV increases the willingness of 

providers to administer a second dose. The AAP COID has approved the drafting of a revised varicella 

immunization statement that recommends a universal second-dose policy. 

State and local health departments have emphasized that an interim strategy of a second dose for 

outbreak control is not efficient. A tremendous amount of resources and time are required to respond to 

outbreaks and breakthrough infections. The increasing prevalence of breakthrough infections has 

affected public confidence in varicella immunization and vaccination programs in general. 

In addition to considering the perspectives of providers, health departments and public, the workgroup 

also made strong efforts to address issues raised during the June 2005 ACIP meeting. In response to 

ACIP’s concerns about cost-effectiveness, the workgroup updated the data analysis. The more recent 

data show that both one- and two-dose varicella vaccination programs would be cost-saving from a 

societal perspective compared to no vaccination. The incremental cost-effectiveness of the second dose 

of varicella vaccine likely falls within the reasonable range. 

In response to ACIP’s concerns about programmatic issues and suggestions to delay the second dose 

until the availability of MMRV, the workgroup notes that MMRV was licensed in the fall of 2005. The cost 

of the vaccine is now known and was factored into the updated cost-effectiveness analysis. In response 

to ACIP’s concerns about the purpose and outcomes of a second dose, the workgroup acknowledges 

several key factors. The immune response is more like that of natural infection. Population-based 

immunity will be increased. The decrease in breakthrough infections will lead to reducing outbreaks and 

transmission to other individuals in schools and families with susceptible adolescents, young adults and 

adults. 

In response to ACIP’s concerns about the priority of a two-dose varicella vaccination program relative to 

other new vaccines under consideration, the workgroup acknowledges several key factors. Hepatitis A 

(HepA) vaccine and other vaccines with successful initial programs were approved for routine 

administration to maintain the success of the program. The proposed two-dose varicella vaccination 

program is a priority due to the accumulation of susceptible high school students, college students and 

young adults into adulthood. The proposed intervention is timely. 

The workgroup identified the advantages and disadvantages of two policy options. Policy 1 would be to 

continue the routine one-dose policy with no changes. On the one hand, no additional costs would be 

incurred. However, modifications to the current policy would need to be considered to determine whether 

two doses should continue to be recommended in outbreaks. CSTE informed the workgroup that efforts 

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ACIP Meeting Minutes June 29-30, 2006 Page 30 

to implement ACIP’s 2005 recommendation were not effective at state and territorial levels. CSTE would 

be in a position of reconsidering the feasibility and purpose of case-based surveillance. 

On the other hand, ongoing outbreaks require a tremendous amount of resources from state and local 

health departments. Two doses are not effective for outbreak control. The 2010 goal of a 90% reduction 

in varicella disease may not be achieved or maintained. The accumulation of susceptible persons may 

result in increased disease among adolescents and adults. Confidence in the vaccination program may 

be lost. 

Policy 2 would be to change the recommendation to include a routine second dose. On the one hand, 

data show a 3.3-fold reduction in attack rates among children who received two doses. Cellular and 

humoral immunity would be improved, providing immunity similar to that obtained through natural 

infection. Studies have demonstrated that two-dose effectiveness remains stable and high over 10 years. 

The two-dose program is cost-saving compared to no vaccination. On the other hand, the incremental 

cost is high and the duration of vaccine-induced immunity after two doses is still unknown. Data are 

available for up to 10 years, but lifetime immunity in the absence of external boosting is unknown. 

The workgroup reached consensus on a policy change for a routine two-dose varicella vaccination 

program with catch-up provisions. The advantages of catch-up vaccination are the ability to target the 

current disease burden (schoolchildren with the highest incidence of outbreaks) and capacity to immunize 

susceptible children prior to adulthood. The disadvantage would be the incremental cost of catch-up 

vaccination. However, the workgroup noted that catch-up vaccination can be implemented during routine 

healthcare visits and through school and college entry requirements. 

Dr. Guris described the rationale and data to support the workgroup’s consensus on three programmatic 

issues. One, the workgroup reached consensus on changing the age of the first dose of varicella vaccine 

to 12-15 months. A discrepancy exists between the current recommended ages of the first dose of MMR 

at 12-15 months and varicella at 12-18 months. The proposed change will harmonize the schedule with 

that of measles, mumps and rubella (MMR) and will ease the use of MMRV vaccine. Some studies found 

that vaccination at a young age was a risk factor for vaccine failure, but this limitation will be 

compensated by administration of the routine second dose. 

The workgroup reviewed data from five studies published in 2002-2005 that found early age at 

vaccination to be a significant risk factor for vaccine failure (Dworkin, Haddad, Lee, Vasqyez Verstraeten). 

The 2003 Verstraeten retrospective cohort showed that children vaccinated <15 months of age were 1.4 

times more likely to develop varicella compared to those vaccinated at >15 months of age. The 2005 

Haddad outbreak investigation showed that among children vaccinated >5 years before the outbreak, 

those vaccinated at <18 months of age were 9.3 times more likely to develop varicella than those 

vaccinated at >18 months of age. 

The workgroup also reviewed data from an unpublished prospective cohort study that followed 7,585 

vaccinated children (Black, et al.). Age at vaccination was not found to be associated with a risk for 

developing breakthrough disease. Most outbreak investigations that studied whether age at vaccination 

was associated with an increased risk for vaccine failure did not find age at vaccination to be a risk factor 

for vaccine failure. 

Two, the workgroup reached consensus on routine second-dose administration of varicella vaccine at 4-6 

years of age and permissive use of dose two at an earlier age provided that 3 months have elapsed after 

the first dose. The early second-dose schedule will provide better protection for preschool-aged children. 

However, the proposed schedule is not harmonized with MMR, will not maximize use of the combination 

MMRV vaccine, and may result in lower two-dose coverage until school entry. The schedule would 

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ACIP Meeting Minutes June 29-30, 2006 Page 31 

require extra injections (two VARIVAX or one ProQuad). The impact on current disease burden would be 

delayed. 

The later second-dose schedule will not require an extra injection if ProQuad is used. School entry 

vaccination for measles will provide an opportunity for high vaccination coverage. The impact on the high 

incidence in schools will be seen more rapidly and protection will be provided to younger children through 

impact on school outbreaks and herd immunity. However, some children will have a delay in achieving a 

protective immune response due to the delay in second-dose administration. 

The workgroup reviewed VARIVAX immunogenicity data of an early second-dose schedule (Ngai, Kuter)

and a later second-dose schedule (Watson). In the early second-dose schedule with 1,647 participants, 

the GMT and mean stimulation increased from 12.5 and 44.72, respectively, after dose one to 142.6 and 

67.69, respectively, after dose two. In the later second-dose schedule with 419 participants, the GMT 

and mean stimulation increased from 25.7 and 40.3, respectively, after dose 1 to 218.8 and 58.6, 

respectively, after dose 2. 

The workgroup also reviewed unpublished Merck data on ProQuad immunogenicity that compared early 

and later two-dose schedules and demonstrated high antibody levels. In both schedules, 99% of children 

had >5 gp ELISA units after dose two and GMTs were high after dose two as well. The data review 

showed no substantial differences regarding immune response. The major issues seen were 

programmatic, such as coverage, extra injections and the impact on disease burden. 

Three, the workgroup reached consensus on maintaining a three-month minimum interval for routine 

administration of two varicella-containing vaccine doses. However, dose two does not need to be 

repeated if dose two was administered after at least 28 days following dose two. Several issues were 

discussed related to this decision. 

Despite the availability of a combination MMRV vaccine, minimum intervals between two doses of MMR 

and varicella vaccines are different for persons <13 years of age. The discrepancy between a four-week 

minimum interval for MMR and a three-month minimum interval for varicella will create confusion in the 

field. This discrepancy also facilitates waste because administration of the second dose of varicellacontaining vaccine four weeks after dose one will not be considered a valid second dose and the child will 

be re-vaccinated. Moreover, children may need two MMR-containing vaccines with as short an interval 

as possible in certain situations, such as measles, rubella or mumps outbreaks, prior to travel or before 

school entry. These special situations would also create confusion, limit the use of MMRV or lead to 

unnecessary repeat doses. 

The 4-week interval is currently used for persons >13 years of age. Data from a 1995 study that 

compared adults 13-19 years of age vaccinated at 4- versus 8-week intervals showed that GMTs were 23 

in the 4-week interval group and 30.1 in the 8-week interval group (Kuter, et al.). However, the vaccine 

dose used in the study is lower than the currently licensed dose. A recommendation with a 4-week 

interval between the two doses will be harmonized with MMR, prevent unnecessary repeat doses and 

reduce vaccine waste. ACIP’s general recommendations currently allow vaccination with two parenteral 

live vaccines at least 28 days apart. The shorter interval will also facilitate rapid immunization of children 

for school entry and travel. Studies were conducted for children with a 3-month interval to fit the routine 

well child visit schedule and not for other reasons. However, the 4-week interval is an off-label 

recommendation. No data have been evaluated on an interval <3 months in children. 

ACIP members made several comments on the workgroup’s proposed changes to the varicella 

vaccination policy. Dr. Lieu was hesitant about the catch-up strategy because catch-up vaccination is 

typically less cost-effective than the overall program. Catch-up vaccination will most likely be 

implemented with varicella as a stand-alone dose rather than MMRV. However, she was unsure of the 

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ACIP Meeting Minutes June 29-30, 2006 Page 32 

rationale in recommending a routine second dose and then allowing the unvaccinated group to become 

older without the protection of a second dose. Moreover, the extra number of injections for the target age 

groups will require more nursing administration time. However, Dr. Lieu’s overall position was that catchup vaccination would most likely be beneficial even if the strategy is less cost-effective. 

Dr. Hull conveyed that a recommendation of a two-dose policy without catch-up vaccination would not be 

beneficial from a state public health perspective. State epidemiologists are charged with controlling 

outbreaks, responding to criticism and concerns by anxious parents, and addressing the long-term 

potential of children who will be hospitalized with varicella pneumonia as adults. His position was that 

ACIP should not recommend a two-dose policy without catch-up vaccination. 

Dr. Hull also urged ACIP to harmonize the schedule with MMR to reduce the burden on parents, 

physicians and public health clinics. If ACIP recommends a 3-month interval, studies should be rapidly 

conducted to decrease the interval to one month. Dr. Kuter confirmed that Merck is planning to initiate 

studies on a one-month interval in the fall of 2006. She also pointed out that the varicella vaccine has 

been recommended for routine use in Europe as MMRV with administration of two doses as early as 

possible, with a minimum interval of one month, and a maximum interval of three months. Merck will use 

the European data on all four components of the MMRV vaccine to support its upcoming studies. 

Dr. Cody Meissner, the AAP liaison, announced that COID is currently revising AAP’s varicella statement. 

A recommendation will be made for universal administration of a second dose of varicella-containing 

vaccine for children 12 months-12 years of age. A second dose will also be recommended for 

adolescents and young adults who previously received one dose before 13 years of age. 

AAP’s updated statement will focus on four key points. One, the first dose of a varicella-containing 

vaccine should be routinely administered at 12-15 months of age. This recommendation represents a 

change from 12-18 months and is being made to facilitate use of MMRV at the age presently 

recommended for administration of MMR. Two, the second dose of a varicella-containing vaccine should 

be routinely administered at 4-6 years of age or at least three months after dose 1. The interval may be 

as short as 28 days if administration of dose 2 is necessary at an earlier interval, such as during a 

measles or mumps outbreak. 

Three, catch-up immunization will be addressed by recommending that all children entering elementary, 

middle, and high school, and college should have received two doses of varicella-containing vaccine 

unless other evidence of immunity to varicella is presented. Four, the preference for use of the MMRV 

combination vaccine whenever possible will be encouraged. 

In 2005, COID concluded that a second dose is critical for improved control of the burden of disease due 

to varicella and unanimously voted in favor of a recommendation for a second dose. COID is now 

awaiting ACIP’s decision on a second dose for the target age group because disparate recommendations 

among professional organizations will lead to confusion. Dr. Meissner emphasized that AAP hopes ACIP 

will now endorse routine and catch-up recommendations for a second dose to facilitate the 

implementation of uniform recommendations by AAP, ACIP and the American Academy of Family 

Physicians (AAFP). 

Dr. Samuel Katz, the Infectious Disease Society of America liaison, strongly supported a second dose of 

varicella vaccine. However, he cautioned ACIP against comparing measles and varicella because the 

immunopathogenesis of the two diseases is entirely different. He also advised ACIP to convey clearly to 

the public that unlike measles, varicella will not be eliminated in the United States by a two-dose 

schedule. 

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Dr. Abramson added that a two-dose schedule will decrease rather than eliminate breakthrough disease. 

This understanding will avoid a false sense of failure when breakthrough disease is still present in the 

future. Dr. Philip Brunell, of NIH, agreed with these comments based on the existing data. He asked 

ACIP to consider recommending a 4-in-1 dose for children 12-15 months of age and a second dose for 

children and adults who previously received only one dose. 

Dr. Doug Campos-Outcalt, the AAFP liaison, was uncertain of the advantages in recommending a second 

dose of varicella vaccine at an earlier age than MMR. This change will complicate several issues, such 

as an increased number of injections, vaccine storage and the overall schedule. If ACIP recommends an 

earlier age for the second dose of varicella vaccine, however, he supported harmonization with the 

second dose of MMR. Dr. Campos-Outcalt expressed an interest in reviewing mathematical modeling 

data on children <4 years of age. 

Drs. Kuter and Florian Schödel of Merck provided additional details in response to ACIP’s questions. 

• Merck reviewed studies on the second dose of varicella vaccine to distinguish between 

persons who did and did not respond to the first dose. The data showed the following 

results. Some persons were primary vaccine failures. GMTs showed that persons who 

failed to respond after dose 1 clearly responded after dose 2. This trend occurred in 99% 

of persons with titers <5, but GMTs of this cohort were not as high as the group that 

obtained a take after dose 1. Merck committed to sharing these data with ACIP. 

• The potency of the vaccine has remained the same since licensure. Merck has 

conducted numerous studies and found that seroprotection is slightly lower than 

seroconversion after a single dose. Seroprotection (a threshold >5 gp ELISA) was 

relatively lower than the high seroconversion rate of 90%. However, seroconversion 

rates do not correlate as well with the absence of breakthrough disease compared to 

seroprotection. More breakthrough disease is seen with seroconversion alone, but at a 

very low titer. 

ACIP Vote on the Varicella Vaccination Policy 

Recommendation 1 proposes a change in the current varicella vaccination policy. Children would be 

routinely vaccinated with two doses at 12-15 months of age for dose 1 and 4-6 years of age for dose 2 

with the following caveat: “The second dose can be administered at an earlier age provided the interval 

between the first and second dose is at least three months. However, the second dose does not need to 

be repeated if the second dose was administered after at least 28 days following the first dose.” 

Dr. Abramson called for a motion on the proposed recommendation. Dr. Campbell moved as follows: 

“ACIP adopts a routine two-dose varicella vaccination policy as outlined by the workgroup.” The motion 

was seconded by Dr. Finger and passed by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Recommendation 2 is on catch-up vaccination. “To improve individual protection against varicella and for 

more rapid impact on school outbreaks, second-dose catch-up varicella vaccination is recommended for 

children, adolescents and young adults who previously received one dose. Catch-up vaccination can be 

ACIP Meeting Minutes June 29-30, 2006 Page 33 

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implemented during routine healthcare provider visits and through school and college entry 

requirements.” 

In response to Dr. Turner’s questions, Dr. Seward pointed out that issues related to varicella vaccination 

of healthcare workers (HCWs) and pregnant women are covered in ACIP’s varicella prevention 

statement. The workgroup would address vaccination of HCWs during its update on the evidence of 

immunity to varicella. With respect to pregnancy, the current recommendation is for providers to question 

patients about pregnancy. CDC and Merck have been jointly operating a varicella vaccine in pregnancy 

registry for the past ten years. No congenital varicella syndrome or adverse outcomes have been 

reported to date based on ~600 notifications to the registry on women who inadvertently received the 

vaccine during pregnancy. However, varicella vaccine is contraindicated during pregnancy. 

ACIP suggested that recommendation 2 be changed to “young adults through 22 years of age” or “adults” 

rather than “young adults.” 

Dr. Abramson called for a motion on the proposed recommendation. Dr. Campbell moved as follows: 

“ACIP adopts the policy for catch-up varicella vaccination with the revision of deleting ‘young’ and stating 

‘...for children, adolescents and adults who previously had one dose.’” The motion was seconded by Ms. 

Stinchfield and passed by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Dr. Guris reported that the workgroup reviewed comments from state health departments to make the 

following revisions to the evidence of immunity in the ACIP varicella prevention statement. The following 

are criteria for evidence of immunity: (1) documentation of age-appropriate vaccination: one dose for 

preschool-aged children >12 months and two doses for school-aged children, adolescents and adults; (2) 

laboratory evidence of immunity or laboratory confirmation of disease; (3) born in the United States before 

1980; (4) a healthcare provider diagnosis of varicella or verification of history of varicella disease; and (5) 

history of herpes zoster based on healthcare provider diagnosis. 

The workgroup changed the previous cutoff point of 1965 to “born in the United States before 1980” 

based on new national seroprevalence data that suggest persons born between 1965-1980 have a 

susceptibility rate between 2.6%-2.8%. The following footnote was added to the new cutoff. “Healthcare 

facilities should consider recommending varicella vaccine for HCWs born before 1980 and without 

evidence of immunity.” 

The workgroup clarified “verification” by adding the following footnote to “a healthcare provider diagnosis 

of varicella or verification of history of varicella disease.” “Verification can be done by a clinician (e.g., a 

school or occupational clinic nurse, physician assistant or physician). For atypical and/or mild disease 

history, epi-link to a typical varicella case or evidence of laboratory confirmation at the time of acute 

disease should be sought.” This language is intended to increase specificity about breakthrough disease 

and give clearer guidance to providers who will assess children for evidence of immunity. 

 

The workgroup clarified the previous language on vaccination of human immunodeficiency virus- (HIV) 

positive children. ACIP’s previous vote on the vaccination of HIV-infected children with CD4 Tlymphocytes >15% did not specify the clinical classification. The revised language states that “single 

antigen varicella vaccine should be considered for HIV-infected children in CDC class N2, A2 or B2 with 

CD4+ T-lymphocytes >15%.” 

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Dr. Kathleen Neuzil, the American College of Physicians (ACP) liaison, reiterated her previous concern 

that varicella vaccine is contraindicated in HIV-positive adults, as per guidance provided inthe adult 

immunization schedule. Dr. Seward confirmed that CDC is attempting to gather data from correctional 

facilities and other settings to address this issue. In response to Dr. Campos-Outcalt’s question, Dr. 

Seward and Dr. Schödel clarified that “single antigen varicella vaccine” is recommended due to the 

absence of data on MMRV. Merck has not produced data to support the use of ProQuad in 

immunocompromised children. 

The following suggestions were made to refine the language on vaccination of HIV-positive children. A 

footnote should be added to clarify that single antigen varicella is recommended due to higher titers of 

VZV in MMRV and the absence of any data on MMRV. The language should be revised to “N2, A2, B2 or 

better.” 

Dr. Abramson called for a motion on the proposed recommendation. Dr. Campbell moved as follows: 

“ACIP adopts the revised varicella prevention statement with the following additional edits. A footnote will 

be added to clarify that single antigen varicella is recommended due to higher titers of VZV in MMRV and 

the absence of any data on MMRV. The language will be changed to ‘N2, A2, B2 or better.’” The motion 

was seconded by Dr. Gilsdorf and passed by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

Proposed VFC Resolution 

Dr. Gregory Wallace, of CDC, reported that the purpose of the resolution is to incorporate changes for the 

use of measles, mumps, rubella and varicella-containing vaccines. A two-dose schedule is being 

recommended for varicella-containing vaccine and the indication for the MMRV formulation is being 

updated. The workgroup agreed to cite the immune globulin table published in the Morbidity and Mortality 

Weekly Report (MMWR) rather than reproduce the table in the VFC resolution. 

The first dose of varicella vaccine would be administered at 12-15 months of age and the second dose at 

4-6 years of age. A footnote was added to the minimum interval to clarify that for persons <13 years of 

age, the second dose does not need to be repeated if the second dose was administered after at least 28 

days following the first dose. ACIP’s recommended language on immune status and children with a CD4 

count >15% was incorporated. Administration of MMRV is not recommended as a substitute for the 

component vaccine when vaccinating HIV-infected children. The recommended ages for MMRV will be 

changed to 12 months “through” 12 years rather than “to” 12 years. 

The following language is being incorporated to reflect ACIP’s discussion on catch-up vaccination. 

“MMRV may be administered when a dose of MMR or varicella vaccine is indicated (first dose or second 

dose). MMRV should not be administered for the second dose of MMR or varicella except when both are 

indicated or if no MMR or varicella vaccine is available at the time the dose is indicated.” 

ACIP Vote on the Proposed VFC Resolution 

ACIP Meeting Minutes June 29-30, 2006 Page 35 

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The following suggestions were made to refine the VFC resolution. A caveat should be added to the 

recommendation to use a single component. The language should clarify the higher varicella antigen 

content and the absence of data on MMRV. The general recommendations should be cited for the 

antibody table because this information includes more recent data in 2002. 

Dr. Abramson called for a motion on the proposed VFC resolution. Dr. Campbell moved as follows: 

“ACIP approves the proposed VFC resolution. The motion was seconded by Ms. Stinchfield and passed 

by a majority vote. The disposition of the vote is as follows: 

• 13 in favor: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, 

Morita, Morse, Stinchfield, Womeodu. 

• 2 with conflicts: Poland, Treanor. 

• 0 opposed. 

INFLUENZA VACCINE 

The series of presentations and ACIP’s discussion and vote on the influenza vaccine are set forth below. 

Next Steps in Decreasing Influenza-Associated 

Morbidity and Mortality Through Annual Vaccination

Dr. Ban Allos, the Influenza Workgroup Chair, reviewed the current burden of influenza disease; 

summarized the existing influenza vaccination target groups; and described future options to expand the 

annual recommendations for influenza vaccination. Of the U.S. population, 5%-20% is infected with 

influenza each year with the highest rates of infection among children. Of >200,000 hospitalizations 

annually, most occur in persons >64 years of age. Hospitalization rates in children <2 years of age are 

similar to those among adults >65 years of age. 

Influenza is the number one cause of vaccine-preventable disease in the United States. Of >36,000 

deaths caused by influenza each year, >90% occur in adults >65 years of age. A study published in 1996 

showed that the highest illness rates occur in children 5-14 years of age (Sullivan). A study published in 

2004 showed that the greatest rates of hospitalization per 100,000 person years occur in persons >65 

years of age and children <5 years of age (Thompson). The large majority of influenza-associated deaths 

occur in persons >65 years of age. 

ACIP currently recommends annual vaccination for persons at increased risk of severe complications 

from influenza and those who live with or care for these persons. Routine vaccination is also permissive 

for the general population. The groups recommended for annual influenza vaccination increased from 

~80 million persons in 1964 to 218 million persons in 2006. The influenza vaccination target groups now 

represent 73% of the total U.S. population and include: 

• Children aged 24–59 months; 

• Children and adolescents (aged 6 months-18 years) who are receiving long-term aspirin 

therapy and, therefore, might be at risk for experiencing Reye’s syndrome after influenza 

virus infection; 

• Women who will be pregnant during the influenza season; 

• Adults and children who have chronic disorders of the pulmonary or cardiovascular 

systems, including asthma (hypertension is not considered a high-risk condition); 

• Adults and children who have required regular medical follow-up or hospitalization during 

the preceding year because of chronic metabolic diseases (including diabetes mellitus), 

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renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications or by HIV); 

• Adults and children who have any condition (e.g., cognitive dysfunction, spinal cord 

injuries, seizure disorders, or other neuromuscular disorders) that can compromise 

respiratory function or the handling of respiratory secretions or that can increase the risk 

for aspiration; 

• Residents of nursing homes and other chronic-care facilities that house persons of any 

age who have chronic medical conditions; 

• Persons aged 50-64 years; 

• Persons aged >65 years; 

• Healthy household contacts and caregivers of children 0-59 months of age and persons 

at high risk for severe complications from influenza; and 

• HCWs. 

The limitations of the current risk-based strategy include confusing recommendations. The 12 different 

influenza vaccination target groups are difficult for both healthcare providers and patients to remember. 

The complicated system may play a role in low coverage levels among the target groups. NIS data 

showed that 7.4% of children 6-23 months of age received >1 influenza vaccine doses and 4.4% were 

fully vaccinated during the 2002-2003 influenza season. Vaccination levels in this population during the 

2003-2004 influenza season were 17.5% with >1 influenza vaccine doses and 8.4% with full vaccination 

(the second year of ACIP encouragement). Self-reported data from the National Health Interview Survey 

showed that coverage levels in most adult target groups between 1989-2004 were far below the Healthy 

People 2010 goal for influenza vaccination. 

Several options can be considered to further reduce the burden of influenza. Vaccination levels can be 

increased in the existing target groups by improving public awareness, provider education and practices. 

A universal vaccination policy could be incrementally established with children and more generally with 

adults. Participants of an October 2005 workshop agreed that incremental steps should be taken toward 

an annual universal influenza vaccination policy beginning with children first because this population 

accounts for the highest infection and transmission rates. Moreover, vaccination of children is likely to be 

easier and more feasible compared to other target groups. 

A study published in 1969 showed that the influenza infection rate did not peak in adults in a town with 

vaccinated schoolchildren in grades K-12 compared to a nearby town with no vaccination of the same 

population (Monto, et al.). However, several critical factors must be assessed before changing the 

current recommendations and advancing toward a universal policy. New surveillance systems should be 

developed or existing systems should be enhanced to better evaluate influenza illness. Vaccine 

effectiveness and safety should be monitored. The feasibility of annually vaccinating school-aged 

children and working adults should be assessed. An adequate vaccine supply must be assured. 

The ACIP Influenza Working Group has developed a potential time frame to modify the annual influenza 

vaccine recommendations. Critical issues could be assessed and addressed from 2006-2008. An 

expansion of the recommendation to include all school-aged children 5-18 years could be considered in 

2008-2009. The recommendations could be broadened to include household contacts and caregivers of 

school-aged children from 2010-2011. Universal vaccination could be recommended if necessary and 

the recommendations could be extended to persons 18-49 years of age from 2012-2013. 

During the discussion following the presentation, Dr. Allos noted that efforts are also underway to 

increase influenza vaccination of HCWs. HCWs are now required specifically to decline vaccination. The 

Joint Commission on the Accreditation of Healthcare Organizations reached agreement on a new policy 

for hospitals to collect, report and publish rates of HCW vaccination in local newspapers. 

 

This document has been archived for historical purposes. (7/1/2006)
ACIP Meeting Minutes June 29-30, 2006 Page 38 

Several ACIP members provided input on the workgroup’s proposed timeline for universal vaccination. 

Dr. Morse’s position was that the interval to the target date of 2013 date could be shortened if the 

seasonal strategy was linked to the pandemic influenza plan. He did not believe a universal policy would 

place a tremendous burden on the vaccine supply because the current recommendations now cover 73% 

of the total U.S. population. Dr. Hull pointed out that universal vaccination would essentially be reached 

in 2011 after the recommendations were expanded to include household contacts and caregivers of 

school-aged children. 

Dr. Poland’s position was that the proposed timeline would not decrease confusion among providers and 

the public about influenza vaccination. He also found the interval to the 2013 target date to be 

unacceptably lengthy, because a large segment of the U.S. population will continue to become infected 

with and die from influenza before that time. Dr. Poland expressed concern that the influenza morbidity 

and mortality would result in billions of dollars in direct and indirect costs prior to 2013. Moreover, the 

workgroup’s proposed timeline is risk-based and no evidence has been produced to support these types 

of programs. A faster timeline to a universal policy would actually contribute to an expansion in vaccine 

supply. 

Dr. Poland urged the ACIP to minimize the focus on vaccine safety because this approach decreases 

confidence in and unnecessarily raises concerns about the influenza vaccine. He noted that a five-year 

pilot study of a universal policy in Ontario, Canada resulted in a doubling of vaccination levels in high-risk 

groups and the development of vaccine distribution and administration programs to increase pandemic 

preparedness. Dr. Poland supported a universal policy at this time with an incremental approach to 

emphasize special risk groups. 

Dr. Bruce Gellin, the ACIP ex officio representative for the National Vaccine Program Office (NVPO), 

announced that the HHS Secretary recently awarded >$1 billion to five companies to accelerate the 

development of a cell culture vaccine, licensure of additional seasonal influenza vaccines in the United 

States, and construction of additional manufacturing facilities in the United States. The companies are in 

various stages of development, but HHS expects to see initial progress in 2008. HHS also recently 

awarded ~$100 million a year to sanofi pasteur to accelerate cell culture vaccine production. The ultimate 

goal of these awards is to provide sufficient pandemic vaccine for the entire country. Consideration can 

then be given to an adequate seasonal vaccine supply for the entire country after pandemic needs are 

addressed. 

Dr. Carol Baker, the AAP liaison, supported universal implementation for all existing target groups 

because a universal immunization policy still would not assure vaccination of pregnant women and other 

high-risk populations. She encouraged the ACIP to deliver strong messages about universal 

implementation. Moreover, the public, physicians and all other components of the healthcare community 

should be informed that solid data have been produced that support the administration of annual 

vaccination to the target populations. Dr. Kristin Nichol, the VA ex officio representative, joined the 

meeting by conference call and pointed out that four key strategies have demonstrated effectiveness in 

enhancing immunization levels among HCWs: convenient access, free vaccine, education, and 

leadership by healthcare institution management. 

Mr. Steve Allred, of Get A Flu Shot.com, listed several reasons for ACIP to quickly advance toward 

universal immunization. Manufacturers will reduce production if vaccine is not utilized. The longest 

period of time that has passed between pandemics in the last century has been 39 years. The 1968 

Hong Kong influenza outbreak was the last pandemic. Restrictions placed on vaccine during a shortage 

result in persons in high-risk groups declining vaccination. Mr. Allred emphasized that influenza morbidity 

and mortality rates will remain high if ACIP delays recommending universal vaccination. 

This document has been archived for historical purposes. (7/1/2006)
Mr. John Vittas and Mr. Gary Stein, of Families Fighting Flu (FFF), lost a grandchild and child, 

respectively, to influenza. Both children were >23 months of age and were outside of ACIP’s influenza 

vaccination target group of children 6-23 months of age. FFF deeply thanks ACIP for its February 2006 

recommendation to expand the influenza vaccination target groups to include children 24-59 months of 

age. This recommendation will play a critical role in protecting children and supporting FFF’s mission to 

reduce childhood influenza deaths and raise awareness about the importance of all children receiving 

influenza vaccine. FFF hopes that ACIP will further expand the influenza vaccination target groups to 

include all children in the near future. 

Dr. Abramson announced that ACIP would not vote on the workgroup’s proposed timeline. He advised 

the members to provide Dr. Allos with additional comments and feedback by e-mail. 

Dr. Neuzil summarized recent data on one versus two TIV doses in influenza vaccine-naïve children. 

Immunogenicity data on children <2 years of age are limited, but data on children 2-6 years of age with no 

detectable hemagglutination inhibiting antibody levels show that this population has lower responses than 

children with detectable levels. As a result, pre-existing immunity is significant. Data also demonstrate 

that antibody responses to influenza type B strains resulting from vaccination or infection can be 

substantially lower compared to responses after exposure to influenza type A strains due to vaccination 

or infection. 

One Versus Two Doses of Trivalent Inactivated Influenza Vaccine (TIV) in 

Influenza Vaccine-Naïve Children

A study was published in 2005 to gather more immunogenicity data (Englund). In year 1 of the study, 

children were enrolled in the spring of 2003 and randomized to either receive the 2002-2003 TIV or defer 

vaccination until the fall. The cohort was given one dose with the new season’s vaccine in the fall, but the 

antigen content was the same as the previous year. Antibody responses after two spring/fall doses and 

two fall doses were compared. The year 1 results showed that immunogenicity after two doses was 

superior to one dose. Early administration of the first dose was not inferior to routine administration of the 

first dose in years when antigens do not change. 

The 2003-2004 TIV formulation was not changed in year 2 of the study, but new H3N2 and B antigens 

were added to the 2004-2005 TIV formulation. Three studies were conducted in year 2 with the change 

in vaccine antigens. Study 1 is in press and randomized children 6-23 months of age to receive the first 

dose in the spring versus the first dose in the fall (Walter, et al.). Antibody responses were assessed 

after two doses. The conclusions of study 1 in year 2 are as follows: Immunogenicity after two doses 

was superior to one dose. Post-dose 2 antibody responses were similar between early and standard 

dose schedules when the antigen did not change. Priming was less robust with the drifted H3N2 antigen, 

but ~70% of children still had protective antibody levels. The major change in the B antigen resulted in a 

markedly decreased response after two doses of vaccine. 

Study 2 is in press and was an observational, non-randomized and open-label trial comparing children 6-

23 months of age who received one dose in both the prior and current fall seasons and children who 

received two doses in the current fall season (Englund). The group 1 children were significantly older 

than those in group 2. The conclusions of study 2 in year 2 are as follows. Post-dose 2 antibody 

responses were similar regardless of whether the child received one dose in the prior and current fall 

seasons or two doses in the current fall season when the antigen did not change. The drifted H3N2 

priming made no difference. The major change in the B antigen resulted in a markedly decreased 

response among children who received one dose in the prior and current fall seasons versus those who 

received two doses in the current fall season. 

ACIP Meeting Minutes June 29-30, 2006 Page 39 

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Study 3 is in press and was a prospective open-label trial of one versus two TIV doses in the fall among 

vaccine-naïve children 5-8 years of age (Neuzil). All children in the study received two doses of vaccine. 

Blood was drawn pre-dose 1, post-dose 1 and post-dose 2. The conclusions of study 3 in year 2 are as 

follows. A two-dose regimen in children 5-8 years of age was superior to a one-dose regimen when the 

response to all antigens was considered. Pre-existing antibody was the strongest predictor of antibody 

response. Even after two doses, >33% of children in the study did not have protective responses to the B 

antigen. 

Two published studies showed limited correlation between antibody response data and clinical data in 

children. A 1990 study administered a single TIV dose to children 6-9 years of age and demonstrated 

protection against subsequent laboratory-confirmed influenza B infection (Gruber, et al.). The protection 

was correlated with influenza B neutralizing antibody response. A 2005 retrospective study with 5,000 

children 6-23 months of age estimated vaccine effectiveness of 49% against clinical pneumonia and 

influenza-like illness (ILI) among children who received two TIV doses (Ritzwoller). No effectiveness was 

seen among children who received one dose. The study did not produce immunogenicity data. 

A recent study that analyzed influenza vaccine effectiveness in the 2003-2004 season is in press (Allison, 

et al.). The cohort of children 6-21 months was stratified by those unvaccinated, partially vaccinated with 

one dose, and fully vaccinated with two doses in the same season or one dose in each season. 

Outpatient visits for ILI and pneumonia or influenza served as the primary outcomes. The stratified 

analysis indicated effectiveness against ILI of 82% for children who received two doses in the same year 

and 62% for children who received two doses in different years. 

Overall, one year of data from the recent studies suggest that the current recommendation for children to 

receive one dose in the current year if one dose was obtained the previous year provides adequate 

protection for influenza A and inferior protection for influenza B. However, protection for influenza B may 

be inferior even after two doses and in older age groups. A determination has still not been made on 

whether current efforts to measure influenza B are adequate. 

In response to a question raised by Dr. Treanor, Dr. Neuzil said she would follow-up to determine whether 

a sufficient number of children 6-23 months of age were enrolled in the studies to identify the role of preexisting immunity in this age group. She acknowledged that this analysis was made only in older children 

5-8 years of age. 

Options for Children Who Were Not Fully Vaccinated Initially 

Dr. Nicole Smith, of CDC, presented options for ACIP to consider in vaccinating children <9 years of age 

who received only one dose of influenza vaccine in the first season that they are vaccinated. ACIP’s 

current recommendation of two doses of influenza vaccine for children <9 years of age who have not 

been previously vaccinated is consistent with the evidence. However, compliance with this guidance is a 

continual challenge. COID is considering changing AAP’s guidance to recommend two influenza vaccine 

doses during the subsequent season for children who should have received two doses during an initial 

season, but received only one dose. 

The Influenza Working Group proposed that ACIP consider whether the data are sufficient to justify a 

change in ACIP’s recommendation. The workgroup also requested feedback on strategies to address the 

potential discrepancy between the ACIP and AAP recommendations if ACIP does not approve a change 

in its current guidance and AAP changes its recommendations. CDC’s influenza statement for the 2006-

2007 season recommends only one TIV dose the following season if a child 6 months-<9 years of age 

ACIP Meeting Minutes June 29-30, 2006 Page 40 

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who received influenza vaccine the first time did not receive a second dose of vaccine within the same 

season. CDC’s new influenza statement, which provides information for both TIV and the live attenuated 

influenza vaccine (LAIV), can be viewed at www.cdc.gov/flu. 

The workgroup identified the advantages and disadvantages of two options to facilitate ACIP’s discussion 

and vote. Option 1 would not change the current recommendation. On the one hand, the limitations of 

existing data would be acknowledged, the complexity would be decreased, and the challenges of 

providing two doses to an additional group of vaccine-naïve children would not need to be addressed. On 

the other hand, the current recommendation may result in lost opportunities to better protect children 

against influenza. ACIP and AAP guidance may be inconsistent. 

Option 2 would change the recommendation for children <9 years of age who were not fully vaccinated 

initially to receive two doses in the subsequent season. On the one hand, an opportunity would be 

provided to better protect children against influenza. The potential for inconsistency between ACIP and 

AAP recommendations would be minimized. On the other hand, the change would not fully acknowledge 

the limitations of existing data, particularly the absence of direct evidence on the need to provide two 

doses in the subsequent vaccination season. There was also a concern that providers may be less 

inclined to ensure provision of two doses during the initial vaccination season. The demand on the 

currently limited vaccine supply for young children may increase depending upon the timing of 

implementation. 

ACIP Vote on Options for Children Who Were Not Fully Vaccinated Initially 

Dr. Allos listed several reasons for her opposition to changing the current recommendation at this time. 

Complexities and difficulties associated with influenza vaccination may increase for pediatricians and 

parents. ACIP has not had an opportunity to review, evaluate and identify potential flaws in the 

unpublished studies. AAP has not yet reached a definite decision on its influenza vaccination 

recommendations for the target population. 

Dr. Hull was concerned that a change in the current recommendation would worsen the scheduled 

vaccine shortage for young children in upcoming influenza season. Moreover, no evidence has been 

produced to demonstrate adequate levels of protection for children who received two doses in one year 

and one dose the following year if a major change in the vaccine occurred. Dr. Treanor supported a 

conservative approach in which the current recommendation would be maintained while more data are 

collected to support a change. 

In response to a question raised by Dr. Pickering, Dr. Neuzil clarified that the major difference between 

children 6-23 months and 5-8 years of age in the recent studies was that one dose was sufficient by the 

age of five years with a single antigen vaccine and the H3N2 strain. However, both age groups appeared 

to need two doses to obtain adequate immunogenicity. 

Dr. Keith Powell, the AAP liaison, summarized COID’s conclusions based on its review of the recent 

studies. Two doses are superior to one dose for children. The administration of one dose in two different 

seasons is not optimal with changes in antigen. “Fully vaccinated” should be simply defined as two doses 

in one year due to the different variables that must be considered. COID agreed that children will be fully 

vaccinated by changing the AAP recommendation to two doses in the same season and one dose the 

following season. Dr. Powell expected AAP to adopt COID’s consensus opinion during its meeting in the 

fall of 2006. 

ACIP Meeting Minutes June 29-30, 2006 Page 41 

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Dr. Michael Decker, of sanofi pasteur, pointed out that neither of the two options addresses the relevant 

question of being primed for the currently circulating strain. He supported a year- and strain-specific 

recommendation, but he realized that this strategy would be virtually impossible to implement. Dr. 

Jonathan Temte, the AAFP liaison, emphasized the critical need for ACIP to issue solid guidance that 

balances vaccine supply issues and the feasibility of clinicians to implement the recommendation. He 

noted that compliance with ACIP’s recommendations would decrease among family physicians if the 

guidance changes each year. 

Dr. Melinda Wharton, of CDC, reminded ACIP that the pre-booking process typically occurs before 

decisions are made about the strain selection. An unfeasible situation would occur if pediatricians and 

family physicians who vaccinate children need to place vaccine orders that would depend on knowing 

what strain selection changes were going to occur without that knowledge being available. Dr. Kathy 

Coelingh, of MedImmune, announced that MedImmune published LAIV data on children <9 years of age. 

Children 5-7 years of age in a pediatric trial were randomized to a single dose to address the issue of 

whether one or two doses are actually needed in the same season. The MedImmune data showed 100% 

efficacy with a single dose. The efficacy rate was also 100% when the same cohort was randomized to 

the same treatment regimen of a single dose the following year and the strain drifted. 

Dr. Abramson called for a motion on the options for children who were not fully vaccinated initially. Dr. 

Hull moved as follows: “ACIP accepts option 1 to not change the current recommendation due to the lack 

of data to make a decision at this time.” The motion was seconded by Dr. Allos and unanimously 

approved by all 15 voting members: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, 

Marcuse, Morita, Morse, Poland, Stinchfield, Treanor, Womeodu. 

Dr. Abramson committed to obtaining a ruling on Dr. Treanor’s potential conflict in which the University of 

Rochester is conducting a study for ID Biomedical and this company is owned by GlaxoSmithKline (GSK). 

He also confirmed that ACIP would revisit its vote if AAP issues a different recommendation. 

Options for Tiered Use of TIV 

Dr. Smith presented options for ACIP to consider in the tiered use of TIV in the event of a vaccine 

shortage or delay. Disruptions in vaccine production or distribution have occurred during recent seasons. 

The total influenza vaccine supply for the 2006-2007 season is expected to be ~100 million doses. 

CDC’s new influenza statement advises providers to take advantage of the additional doses by 

developing plans to expand outreach, enhance infrastructure and vaccinate more individuals than the 

previous year. Providers are also encouraged to create contingency plans for the timing and prioritization 

of influenza vaccine in the event of a delay or reduction in supply. 

In February 2006, ACIP approved annual vaccination for children 24-59 months of age, their household 

contacts and out-of-home caregivers. Due to the timing of this recommendation, some providers may not 

have sufficient vaccine for patients <4 years of age. The ACIP/CDC 2005-2006 influenza vaccine 

prioritization statement recommended that state and local health officials and vaccination providers 

prioritize persons in group 1A before all other groups on rare occasions when local vaccine supply is 

extremely limited. The statement also recommended that persons in groups 1A, 1B and 1C be 

considered equivalent and simultaneously vaccinated in all other vaccine shortfall situations. 

Priority groups for influenza vaccine were established to protect high-risk and healthy persons and 

prevent deaths, hospitalizations and other serious complications associated with influenza. The current 

prioritization scheme was published in the summer of 2005 and includes two tiers and three sub-tiers for 

the influenza vaccination target groups. Tiers 1A and 1B are designed to prevent deaths and 

ACIP Meeting Minutes June 29-30, 2006 Page 42 

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ACIP Meeting Minutes June 29-30, 2006 Page 43 

hospitalizations, respectively. Tier 1C is designed to protect high-risk populations with a “cocooning” 

approach by vaccinating household contacts and caregivers of high-risk persons. Tier 2 is designed to 

further implement the cocooning approach and also protect healthy persons. Tier 3 is designed to protect 

healthy persons. 

The Influenza Working Group identified the advantages and disadvantages of four key questions to 

facilitate ACIP’s discussion. First, should the tiers be renumbered with a new prioritization scheme of 

tiers only and no sub-tiers? On the one hand, elimination of the sub-tiers would more clearly express 

prioritization across different groups. On the other hand, the number of tiers would increase to five. 

Second, should prioritization be established between tiers if the sub-tiers are retained? The following 

language could replace the current text if ACIP reaches agreement on this option: “Providers should 

consider prioritizing group 1A before group 1B and group 1B before group 1C on rare occasions when 

local vaccine supply is extremely limited.” On the one hand, “should consider” would allow for discretion 

at the local level. Prioritization between sub-tiers would also acknowledge that a limited supply may not 

permit equal vaccination of groups 1B and 1C. On the other hand, vaccination of group 1B would be 

given a higher priority than group 1C. 

Third, should healthy persons 5-64 years of age be included as one priority group or should adults 50-64 

years of age continue to serve as a separate group? The alternative tier 3 could be “persons 2-64 years 

of age without high-risk conditions” if ACIP reaches agreement on this option. On the one hand, the 

creation of one priority group of adults 50-64 years of age would recognize that healthy persons should 

have a lower priority for receiving vaccine in the event of a shortage. The priority groups would be 

simplified by eliminating the need to distinguish between healthy persons in different age groups with the 

exception of children <5 years of age. On the other hand, the current focus on the need to vaccinate 

adults 50-64 years of age would be eliminated. 

Fourth, what approaches should be taken to include children 24-59 months of age in the priority group 

table? CDC’s new influenza statement for the 2006-2007 season emphasizes the need to prevent 

emergency department and outpatient visits in addition to deaths and hospitalizations. 

The Working Group suggested four specific options for ACIP’s consideration. Option 1 would change tier 

1B with the addition of “children 6-59 months of age” and change tier 3 to “persons 5-64 years of age 

without high-risk conditions.” On the one hand, option 1 would be consistent with the paradigm shift that 

the burden of illness includes emergency department and outpatient visits in addition to deaths and 

hospitalizations. Healthy persons 5-64 years of age would be grouped in one tier. On the other hand, the 

relative prioritization of children 6-23 months versus children 24-59 months of age would not be 

addressed. 

Option 2 would change tier 1C with the addition of “children 24-59 months of age” and change tier 3 to 

“persons 5-64 years of age without high-risk conditions.” On the one hand, option 2 would group healthy 

persons 5-64 years of age in one tier and address the relative prioritization of children 6-23 months 

versus children 24-59 months of age. On the other hand, a sub-tier would be created that combines 

direct prevention of the burden of disease and indirect protection through vaccination of caregivers. 

Option 3 would place “children 24-59 months of age” in a separate tier 1C and change tier 3 to “persons 

5-64 years of age without high-risk conditions.” Household contacts and out-of-home caregivers of 

children <6 months of age and HCWs would be placed in a new tier 1D. On the one hand, option 3 would 

group healthy persons 5-64 years of age in one tier and address the relative prioritization of children 6-23 

months versus children 24-59 months of age. On the other hand, an additional sub-tier would be 

established under tier 1. 

This document has been archived for historical purposes. (7/1/2006)
Option 4 would place “children 24-59 months of age” in a separate tier 1C. Household contacts and outof-home caregivers of children <6 months of age and HCWs would be placed in a new tier 2A. 

Household contacts of children and adults at increased risk for influenza-related complications would be 

placed in a new tier 2B. Tier 3 would be changed to “persons 5-64 years of age without high-risk 

conditions.” On the one hand, option 4 would clearly identify three distinct tiers based on the different 

rationale; group healthy persons 5-64 years of age in one tier; and address the relative prioritization of 

children 6-23 months versus children 24-59 months of age. On the other hand, an additional sub-tier 

would be established under tier 2. 

ACIP Vote on Options for Tiered Use of TIV 

Dr. Allos noted that the confusing and complicated tiering strategy does not contribute to reducing the 

burden of disease due to influenza. She hoped that ACIP would recommend elimination of the entire 

system in the near future. In the interim, however, she supported actions to simplify the priority group 

table and make the recommendations more feasible. Dr. Allos suggested that children 24-59 months and 

children 6-23 months of age be placed in the same tier. Prioritization between tiers should not be 

established. 

Dr. Morita reminded ACIP of the importance of the tiering strategy because the priority group table was 

developed for vaccine shortages rather than routine use. She was in favor of separating children 6-23 

months and those 24-59 months of age due to the critical need to distinguish among death, 

hospitalization, and emergency department and outpatient visits during a vaccine shortage. She also 

supported grouping healthy persons 5-64 years of age in one tier. 

Drs. Campbell and Marcuse expressed concerns about the low prioritization of household contacts and 

caregivers of infants <6 months of age. Although solid evidence has not been produced to date to 

demonstrate that the cocooning approach actually protects this group, it was suggested that household 

contacts and out-of-home caregivers of this population also be placed in tier 1B with pregnant women. 

Infants <6 months of age are at risk for severe disease and should be prioritized. 

Dr. Poland was in favor of simplifying the priority group table by maintaining tiers 2 and 3 and combining 

tiers 1A, 1B and 1C because a vaccine supply of <50 million doses is not likely. Sub-tiers could be 

developed and implemented for worst-case scenarios. He also pointed out the critical need for CDC to 

clearly define “shortage” because the term is interpreted differently at the local level by institutions, 

clinicians and cities. 

Dr. Finger supported an all-numbered tiering system with no sub-tiers that would clearly indicate cutoffs. 

Dr. Lieu was also in favor of renumbering the tiers with no sub-tiers and placing children 24-59 months 

and 6-23 months of age in separate tiers. Dr. Treanor’s position was that no changes should be made to 

the current tiering system other than placing the new influenza vaccination target group of children 24-59 

months of age into a tier. 

Dr. Temte reported that he converted the pandemic tiering system into electronic medical records for use 

in actual clinical practice and found the entire exercise to be simple, feasible and helpful. He 

acknowledged that the tiering system should depend on the epidemiology of influenza. Dr. Decker urged 

ACIP to prioritize children 6-59 months of age because the tiering system has the most relevance for this 

group. 

Mr. Allred encouraged ACIP to place HCWs in tier 1A rather than 1C because a strong healthcare 

infrastructure is required to care for all patients with health issues. HCWs have the greatest number of 

contacts with high-risk persons and are the most likely group to spread infection. Dr. Poland agreed with 

ACIP Meeting Minutes June 29-30, 2006 Page 44 

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this comment because data from two randomized trials showed a decrease in influenza morbidity and 

mortality when HCWs rather than residents of long-term care facilities were vaccinated. Dr. Wallace 

pointed out that regardless of ACIP’s vote, CDC will need to issue guidance to providers who do not have 

an adequate vaccine supply for children three years of age. 

Dr. Abramson called for a motion on the options for tiered use of TIV. Dr. Treanor moved as follows: 

“ACIP will retain the existing tiering system, but will add the new group of children 24-59 months of age to 

tier 1C.” Dr. Gilsdorf seconded the motion. Dr. Abramson clarified that persons in tiers 1A, B and C 

would be treated equally unless a severe shortage occurs. Dr. Wharton requested a change to the 

language in tier 3 to be consistent with the motion, whereby the priority group in tier 3 would be persons 

5-49 years of age without high-risk conditions. The motion passed by a majority vote. The disposition 

of the vote is as follows: 

• 12 in favor: Abramson, Allos, Beck, Campbell, Gilsdorf, Hull, Lieu, Morita, Morse, 

Stinchfield, Treanor, Womeodu. 

• 3 opposed: Finger, Marcuse, Poland. 

 • 0 abstentions. 

ISO Update 

Dr. Robert Davis, the ISO Director, covered the following areas in his report. CDC is committed to 

building a robust vaccine safety activity to maintain pace with the increasing number, combinations and 

complexity of recommended immunizations. ISO was moved from NIP to the CDC Office of the Director, 

Office of the Chief Science Officer in 2005. Several reasons support this transition. Immunizations 

impact nearly all Americans. Public confidence in the benefit and safety of vaccinations is essential to the 

success of the life-saving immunization program. Confidence in immunizations can only be sustained 

through scientific quality, objective recommendations, and the absence of perceived conflicts within and 

outside of CDC. 

CDC took several actions before relocating ISO from NIP. Internal and external input was obtained from 

health professionals, scientists, policymakers and parents. A Blue Ribbon Panel of health and safety 

science professionals was convened in 2004 to provide an independent assessment of ISO’s activities. 

Listening meetings were held in communities throughout the country to obtain additional feedback from 

parents and concerned citizens. ISO is now committed to partnering with other HHS agencies to define 

priorities and an agenda for vaccine safety research and safety monitoring in the United States. ISO will 

continue to communicate with concerned parents, public officials and healthcare professionals to 

emphasize the transparency of CDC’s science and research on immunization safety issues. 

ISO is organized into four major components. First, VAERS is an early warning passive surveillance 

system that detects potential problems related to vaccines. ISO uses VAERS to identify signals and 

generate new hypotheses. Second, VSD is a collaborative network of eight MCOs that collect 

comprehensive medical and immunization histories on >7.5 million persons. ISO is currently conducting 

>24 vaccine safety studies under VSD and has completed >100 vaccine safety studies under the project 

to date. ISO uses VSD to test hypotheses. 

Third, the Clinical Immunization Safety Assessment (CISA) Network is designed to conduct in-depth 

clinical investigations of persons with unusual or severe vaccine AEs. ISO uses the CISA Network to 

identify biological underpinnings of vaccine AEs and create re-vaccination protocols. Fourth, the Brighton 

Collaboration is a global initiative to standardize case definitions and provide a common vocabulary for 

vaccine safety research. ISO uses the Brighton Collaboration to support its other three components. 

ACIP Meeting Minutes June 29-30, 2006 Page 45 

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ACIP Meeting Minutes June 29-30, 2006 Page 46 

Two new policy and communications functions were established in ISO to streamline the presentation of 

scientific data and ensure that consistent messages are delivered. 

ISO’s recent successes with vaccine AEs and vaccine safety are highlighted as follows. The large 

increased risk for intussusception following rotavirus vaccination was rapidly identified. The risk of AEs 

after the second MMR dose was found to be greater at 10-12 than 4-6 years of age. No increased risk for 

multiple sclerosis was seen after administration of the HepB vaccine. Acellular pertussis vaccine was 

found to be safer than whole cell pertussis vaccine. No increased risk for inflammatory bowel disease 

was found after administration of MMR vaccine. No increased risk for type 1 diabetes was seen after 

vaccination. 

ISO will face significant challenges in the future. The rotavirus, HPV, MMRV, Menactra®

, zoster, and 

tetanus, diphtheria and pertussis (Tdap) vaccines will strain capacity to provide active and complete 

surveillance, assure the safety of vaccines and respond to new signals. Coincidental or causal 

relationships will need to be systematically analyzed. The study of Guillain Barré Syndrome (GBS), 

anaphylaxis and other rare AEs will require a larger infrastructure. 

Increased focus will be placed on adolescents and adults in the near future, particularly with 

meningococcal, varicella and HPV vaccines. These vaccines will be administered to groups with health 

profiles that are different than those of traditional populations of relatively healthy persons 0-6 years of 

age. Vaccines will be administered in large scale to adolescents, young adults and older adults with a 

higher increased risk of background disease. Ongoing efforts will need to be made to maintain and 

strengthen public perception regarding vaccine safety. 

ISO will take advantage of key opportunities and fulfill certain obligations to address these challenges. 

NVPO will establish an external advisory panel with diverse stakeholders to obtain broad input on ISO’s 

annual research agenda. Active surveillance of new vaccines will be performed through weekly VSD 

updates and real-time assessments of vaccine safety. The vaccine safety research agenda will be 

extended to the genomics field to increase capacity to identify persons at increased risk and obtain more 

knowledge on populations and subgroups at increased risk for vaccine AEs and vaccine failure. 

GBS following Menactra®

 vaccination is one of ISO’s most recent and high-profile challenges. The 

distribution of Neisseria meningitidis cases from 1991-2005 showed a recent decrease in overall 

incidence, but an increase in disease in adolescents and young adults. Menactra®

 was introduced in 

January 2005 and licensed for use in persons 11-15 years of age with the following expectations. Of all 

meningococcal disease among persons >11 years of age in the United States caused by serogroups C, Y 

or W-135, Menactra®

 would cover 75% of cases. The number of cases prevented would be 2.7-

3/100,000 doses and 4.5-5/100,000 doses if freshmen and freshmen living in dormitories, respectively, 

were vaccinated. 

An April 2006 MMWR article reported eight confirmed cases within six weeks post-vaccination and three 

additional cases with onset >100 days post-vaccination that were not believed to be associated with 

Menactra®

. The total number of reported cases was equal to that expected by chance alone. The 

MMWR article reinforced the recommendations to administer the vaccine to indicated persons and report 

GBS cases that occurred in temporal proximity to vaccination. VAERS data as of May 31, 2006 detected 

ten GBS confirmed cases within six weeks after administration of Menactra®

, including two new cases 

with onsets of two and ten days, respectively, post-vaccination. 

ISO analyzed data from the 2000-2003 Healthcare Cost and Utilization Project national inpatient sample 

of GBS cases. A statistically increased risk for GBS following Menactra®

 vaccination was not seen with 

the ten new cases. The cluster was possibly due to a large number of vaccine doses administered within 

the United States during the summer of 2005, but a true causal relationship could not be ruled out. ISO 

This document has been archived for historical purposes. (7/1/2006)
will use the VSD RCA to analyze all children who are given Menactra®

 each week at eight health 

maintenance organizations and follow all vaccinated persons for 42 days to identify any potential GBS 

cases. As of June 2006, data from VSD and United Health Care did not detect any GBS cases from 

140,000 total Menactra®

 doses administered. 

ISO will conduct a new project under VSD to determine whether an association exists between GBS and 

Menactra®

 and quantify the vaccine attributable risk if a relationship is detected. The administration of 

Menactra®

 and the risk for GBS will be assessed in adolescents from the period March 1, 2005-August 

31, 2008. The project will include a cohort study with data from all VSD sites and several MCOs to 

confirm all GBS cases and compare GBS rates between vaccinated and unvaccinated persons. A casecontrol study will be conducted with the same cases and controls as the cohort study if a signal is 

detected. Medical record reviews and patient interviews will be performed to identify potential 

confounding variables. 

Public Comment Period 

Ms. Lyn Redwood, President of Sensible Action for Ending Mercury-Induced Neurological Disorders, 

made the following comments for ACIP’s consideration. She was deeply concerned about ACIP’s recent 

recommendations for pregnant women, infants and children to receive influenza vaccine. She distributed 

a letter to ACIP in which 15 national organizations are asking ACIP to state a preference for thimerosalfree influenza vaccines to be administered to pregnant women, infants and children as recommended in 

the October 2001 Institute of Medicine (IOM) report. 

Ms. Redwood cited several published studies and listed other reasons to support this request. Adequate 

safety studies were not conducted prior to marketing thimerosal as a vaccine preservative. The history of 

thimerosal as a preservative documents its toxicity and ineffectiveness. AEs from mercury exposure have 

been documented following administration of thimerosal-containing vaccines to infants. Exposure to 

vaccine-level thimerosal crosses the blood brain barrier and results in significant deposition of mercury in 

the brain. 

ACIP’s policy of not stating a preference for thimerosal-free vaccines is not current with international and 

state practices in which four countries and seven U.S. states have banned thimerosal-containing 

vaccines. ACIP’s policy will also minimize provider and public confidence in NVPO. Ms. Redwood urged 

ACIP to place a discussion on thimerosal-free vaccines for pregnant women, infants and children on its 

October 2006 meeting agenda. She announced that her son received 237.5 μg of ethyl mercury in his 

infant vaccines. 

Dr. Julia Whiting, a practicing emergency physician in Charlottesville, Virginia, made the following 

comments for ACIP’s consideration. A large segment of the U.S. population does not trust the influenza 

vaccine for a variety of reasons. Patients are typically shocked upon learning that vaccines contain 

mercury. CDC is in jeopardy of losing the trust of the entire population as public awareness about 

mercury continues to increase. Most notably, CDC data show that only 34% of physicians and nurses 

receive annual influenza vaccination. Dr. Whiting urged ACIP to revisit the thimerosal issue in NVPO as a 

matter of public trust. 

Ms. Lujene Clark made the following comments for ACIP’s consideration. As the parent of a child who 

experienced severe neurological, neurodevelopmental and neurobehavioral symptoms after receiving two 

influenza shots in 2002, she expressed concern about mercury in vaccines. However, she continues to 

firmly believe in the importance of immunization. She described several recent events that are 

contributing to the reduction in public trust of NIP. 

ACIP Meeting Minutes June 29-30, 2006 Page 47 

This document has been archived for historical purposes. (7/1/2006)
During the current meeting, one ACIP member expressed a wish to “take the concern about vaccine 

safety off the table.” Another member publicly disclosed a potential financial conflict of interest with the 

influenza vaccine, but still voted on this issue. Of seven missions outlined in NIP’s policy, mission 

statement and strategic blueprint for success, “vaccine safety” is number 6 only ahead of a “happy work 

environment.” Ms. Clark emphasized that NIP’s mission should be to protect children from horrible 

diseases rather than protecting the program. Parents will not trust NIP until children and science are 

placed before profit and politics. NIP will fail unless ACIP objectively views its behavior and prioritizes 

children. 

Ms. Karen Beauvais made the following comments for ACIP’s consideration. She is the mother of a son 

six years of age who received 277 times more than the amount of mercury allowed by the U.S. 

Environmental Protection Agency (EPA) during his catch-up vaccinations. He virtually discontinued 

speaking after being immunized with double doses of mercury-containing vaccines at 15 months of age. 

Her son does not produce a sufficient amount of glutathione to excrete mercury contained in vaccines 

due to his extremely low cysteine level and deficient and improperly functioning immune system. 

Ms. Beauvais is extremely proud that her son recently completed kindergarten and is now learning to 

read. On behalf of her son and other affected children, however, she implored ACIP to recommend the 

ban of mercury from vaccines because less harmful preservatives can be used. 

Ms. Patti Hawkins made the following comments for ACIP’s consideration. She is the mother of a son 

21 years of age who was diagnosed with autism. The diagnosis is extremely perplexing because the 

medical literature states that autistic symptoms must manifest by three years of age, but her son showed 

no symptoms of autism until 15 years of age after receiving four different booster shots with thimerosalcontaining vaccines on the same day. Prior to this time, her son met or exceeded developmental 

milestones for children in terms of academics, sports and social activities. After the booster shots, he 

virtually discontinued speaking and his academic performance deteriorated. 

A recent brain scan and a battery of neurological, psychiatric and medical tests showed that Ms. Hawkins’ 

son is mercury toxic and has a metabolic disorder and traumatic brain injury. She implored ACIP to 

recommend the ban of thimerosal from vaccines because no studies have been conducted to 

demonstrate the safety of this preservative. 

With no further discussion or business brought before ACIP, Dr. Abramson recessed the meeting at 6:18 

p.m. on June 29, 2006. 

Update on Menactra® Supply and Prioritization 

Dr. Abramson reconvened the ACIP meeting at 8:04 a.m. on June 30, 2006 and yielded the floor to the 

first presenter. 

Dr. Wallace reported that from January-May 2005, FDA licensed Menactra®

; ACIP adopted a 

recommendation and VFC resolution for use of the vaccine; CDC secured a contract to provide the 

vaccine to grantees; and recommendations were published in the MMWR. ACIP recommended 

vaccination for children 11-12 years of age during the routine visit, previously unvaccinated adolescents 

at high school entry, and college freshmen living in dorms and other populations at increased risk of 

disease. 

ACIP Meeting Minutes June 29-30, 2006 Page 48 

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ACIP Meeting Minutes June 29-30, 2006 Page 49 

Due to the initial high demand placed on the vaccine by college freshmen in the summer of 2005, the 

manufacturers instituted order limits, back orders developed, and CDC emphasized the current 

recommendations. Sanofi pasteur compiled insurance claim data through August 20, 2005 that showed 

Menactra®

 was preferentially administered to persons 18 years of age compared to other adolescent age 

groups where vaccine use was equally distributed. Insurance claim data through March 26, 2006 showed 

that other age groups caught-up to persons 18 years of age, but emphasis was still not being placed on 

the target groups of children 11-12 years of age and adolescents at high school entry. 

CDC data on the first year of Menactra®

 distribution showed the popularity of and tremendous interest in 

the vaccine because more doses were administered by the private sector than the public sector. In year 

1, ~4.2 million doses were distributed and complaints and concerns decreased in the fall and winter. The 

manufacturer projects production of ~6 million doses in year 2. However, the summer demand is 

expected to be higher than year 1 and approximately an equal number of doses during the summer are 

projected. 

CDC convened a workgroup with representation by AAP, AAFP, ACHA, ACIP, FDA, sanofi pasteur and 

the Society for Adolescent Medicine (SAM) that recommended temporary deferment of vaccination for 

children 11-12 years of age due to the limited supply expected during the summer. The 

recommendations continue to prioritize adolescents at high school entry and college freshmen living in 

dorms who are at higher risk for disease as well as other high-risk groups. The notice was published in 

the MMWR on May 19, 2006. 

CDC’s lessons learned from previous supply issues emphasized the importance of open communications 

with stakeholders to markedly improve interventions. However, CDC acknowledges that the 

implementation of new vaccines and recommendations is increasingly complicated. Supply and demand 

are often unpredictable and responses need to be dynamic and transparent. CDC will continue to hold 

biweekly calls with the stakeholder workgroup to monitor supply and demand. Routine recommendations 

will be re-instituted after supply and demand issues improve. The use of Menactra®

 will be reevaluated in 

response to the interim recommendations. 

Dr. Finger commended CDC for maintaining control of the Menactra®

 supply and prioritization issues. He 

did not interpret the current situation with adolescents 11-18 years of age as non-compliance with the 

recommendations due to the variation in ages upon high school and college entry. He viewed CDC’s 

actions in response to these issues as successful. Dr. Amy Middleman, the SAM liaison, urged CDC to 

enhance the adolescent immunization platforms. This approach will result in stronger capacity to effect 

changes in more discrete packages in the future. 

Dr. Abramson described three issues ACIP will need to consider and address in the future. First, 

pediatricians have sent letters to ACIP and AAP expressing concerns about an “ethical quandary” 

because Menactra®

 is not available to immunize children in the recommended target groups. Second, the 

public has unfairly blamed sanofi pasteur due to a misunderstanding about events that actually caused 

the limited vaccine supply. Third, ACIP’s recommendations must be revisited by the ACIP Meningococcal 

Workgroup because FDA will most likely approve use of the vaccine for a lower age range. Dr. Marcuse 

agreed that the discrepancy between supply and demand in ACIP’s recommendations has created a 

tremendous amount of anguish among parents and damaged ACIP’s credibility. 

Dr. Philip Hosbach, of sanofi pasteur, confirmed that FDA is currently considering the recommendation for 

use of Menactra®

 in children 2-10 years of age. FDA will most likely make a decision in the summer of 

2006. In response to Dr. Katz, representatives for Emergent BioSolutions, Novartis Vaccines, sanofi 

pasteur and Wyeth Vaccines all confirmed that these manufacturers have active meningococcal vaccine 

programs, including vaccines against meningococcal B. 

This document has been archived for historical purposes.
Tdap VACCINE IN PREGNANT WOMEN 

The series of presentations and ACIP’s discussion and vote on the use of Tdap vaccine in pregnant 

women are set forth below. 

Pertussis Workgroup Report 

Dr. Dale Morse, the Pertussis Workgroup Chair, highlighted the workgroup’s recent activities. The 

workgroup initiated its deliberations in June 2004; two Tdap vaccines were licensed in 2005; and ACIP 

adopted recommendations for the use of Tdap in adolescents, routine use in adults, a cocooning 

approach to protect infants by vaccinating adults around the infants, and use of Tdap in HCWs. The 

workgroup was charged with evaluating the safety and efficacy of Tdap during pregnancy and is now 

presenting draft recommendations for ACIP’s consideration. The workgroup specifically focused on 

whether the administration of Tdap would provide passive antibody protection to the infant or interfere 

with the infant’s antibody response to Tdap immunization. 

The workgroup fulfilled its charge by obtaining expertise from 25 members representing ACIP, various 

federal agencies, and 16 consultants representing state health departments, academia and a diverse 

group of professional organizations. The members and consultants reflect a wealth of clinical experience, 

extensive backgrounds, and a strong interest in protecting the lives and health of pediatric and obstetric 

clients. 

The workgroup systematically and scientifically reviewed the major issues related to the safety and 

efficacy of Tdap during pregnancy, but was challenged in reaching consensus. The subject matter is 

tremendously complex and the scientific evidence is limited. Individual opinions among the workgroup 

members ranged from no immunization during pregnancy to no restriction and the promotion of Tdap 

during pregnancy. Of the entire workgroup, approximately two-thirds supported a conservative approach 

and emphasized the need to gather additional scientific data, while approximately one-third favored a 

pragmatic strategy based on existing clinical knowledge and experience. 

The workgroup has continued to work toward consensus and toward providing the best document 

possible for ACIP’s consideration given the current levels of clinical knowledge and scientific uncertainty. 

Due to existing gaps in the scientific literature, the workgroup strongly urges funding of necessary 

research to facilitate the development of definitive and evidence-based guidance in the future. 

Considerations for Tdap in Pregnant Women 

Dr. Trudy Murphy, of CDC, outlined the rationale for considering Tdap in pregnant women; described 

concerns about interference with the infant immune response to DTaP by maternal antibody; presented 

alternatives to Tdap during pregnancy; and summarized results of the Pertussis Workgroup survey. The 

primary reason to consider Tdap in pregnant women is to prevent the morbidity of pertussis during 

pregnancy. Although the morbidity from pertussis is substantial at any age, studies limited to 1981 and 

1993 reported no increase in morbidity or adverse outcomes from pertussis in pregnant women 

(MacLean and Beiter, respectively). 

ACIP Meeting Minutes June 29-30, 2006 Page 50 

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ACIP Meeting Minutes June 29-30, 2006 Page 51 

Secondary reasons to consider Tdap in pregnant women are to decrease mother-to-infant transmission of 

pertussis in early life and to protect infants from pertussis through maternal antibodies passively 

transferred via the placenta. Mothers are the identified source of pertussis in 15%-20% of reported infant 

cases <6 months of age; the source is unknown for >55% of cases (Bisgard, et al.). The ability of 

maternal antibodies induced by Tdap to protect infants from pertussis in early life is unknown. 

A study published in 1946 raised the possibility that infants might receive passive protection from 

maternal antibody (Cohen). For one year, this study followed a cohort of unvaccinated infants whose 

mothers were hyper-immunized with six doses of crude B. pertussis vaccine administered during the 

second trimester of pregnancy. The infants appeared to be protected for ~6 months. When routine infant 

and childhood vaccination was recommended in the late 1940s, vaccination of pregnant women to protect 

infants was abandoned because of concerns that maternal antibody would interfere with the infant’s 

active immune response to DTP vaccination. 

Interference with the infant response to DTP vaccines has been demonstrated in several studies (e.g., 

Van Savage and Englund, published in 1990 and 1995, respectively). Interference was found to occur at 

relatively low maternal antibody titers in women not vaccinated since childhood and after the infant had 

been immunized with three DTP doses. Effects for some antigens were larger when infants were 

vaccinated with whole cell pertussis rather than acellular pertussis vaccine, but variations were seen 

based on the type of pertussis antigen and type of acellular pertussis vaccine. 

The significance of interference on infant protection is unknown, but maternal antibody titers are likely to 

be substantially higher after Tdap during pregnancy than in most women who have not received booster 

pertussis vaccination. No information in pregnant women vaccinated with Tdap is available. The Adult 

Pertussis Trial (APERT) published in 2004 examined pertussis antibody titers among 200 non-pregnant 

subjects 15-65 years of age who received either HepA or acellular pertussis vaccine that did not contain 

tetanus and diphtheria toxoids (Le). In the HepA vaccine group, mean titers of anti-pertussis toxins (antiPT) were low during the 18-month follow-up period. In the pertussis vaccine group, titers of anti-PT 

peaked in the one-month post-vaccination period, dropped at six months and remained relatively stable 

above baseline for over one year. If the response to Tdap in pregnant women is similar, early protection 

of the infant by passive maternal antibody and later interference with the infant immune response to 

DTaP are possible. 

An article published in 2003 demonstrated the hypothetical influence of higher titer maternal antibody on 

the infant’s response to DTaP (Siegrist). Maternal antibody at high titer might provide protection to 

infants, but the antibodies would likely mask the vaccine antigen binding sites so that the infant’s B cells 

could not respond. At low titer, the binding sites would no longer be masked by maternal antibody and 

the infant’s B cells would see the sites and mount a protective response to subsequent doses of DTaP 

vaccine antigens. Partial masking of binding sites would create a situation in which the infant might be 

without protection from maternal antibody or from DTaP vaccination and might be more susceptible to 

pertussis. 

The proportion of reported infant pertussis deaths by month of age in the pre-vaccine era (7,125 U.S. 

infants from 1938-1945 [Sako]) showed that deaths peak in the second and third months, but continue 

throughout the first year of life. From the proportion of reported infant pertussis deaths by month of age 

during the last five years (92 U.S. infants from 2000-2004 [CDC unpublished data]) and from other 

studies, two doses of DTaP vaccine reduce deaths and hospitalizations from pertussis by as much as 

80%. This protective response after one or two doses of infant DTaP is achieved in the setting of low 

maternal titers of antibody to pertussis. 

No data have been collected to date on the safety, immunogenicity and efficacy of Tdap in pregnant 

women. Tetanus and diphtheria toxoids (Td) and tetanus toxoid (TT) vaccines are safe in pregnant 

This document has been archived for historical purposes.
ACIP Meeting Minutes June 29-30, 2006 Page 52 

women and effective in preventing maternal and neonatal tetanus based on many years of experience. 

No increase in pregnancy AEs is anticipated from adding pertussis antigens to Tdap. The 

immunogenicity and efficacy of Tdap in pregnant women are expected to be similar to what has been 

found for non-pregnant adolescents and adults. 

Effective alternative strategies to prevent pertussis in early infancy are available. Antibiotic prophylaxis 

for the mother, infant and household contacts has demonstrated effectiveness in preventing infant 

pertussis when the mother is suspected of having pertussis at delivery (Granström, 1987). ACIP 

recommended a cocoon approach in October 2005 encouraging Tdap vaccination pre-conception; 

postpartum as soon as feasible in conjunction with vaccination of household contacts of infants <12 

months of age; and for mothers with no previous vaccination. A rise in maternal antibodies is expected 

within seven days post-vaccination when Tdap is given in the immediate postpartum period (Halperin, 

2003). On-time DTaP vaccination remains the most effective measure to decrease morbidity and prevent 

mortality from pertussis among infants. 

In summary, data supporting use of TIV include evidence that pregnant women with influenza have 

increased fatality rates; the safety and immunogenicity of TIV have been studied in >2,000 women; and 

the age of first infant dose of TIV is six months after decline in maternal antibody. By contrast, pregnant 

women with pertussis are not known to have increased morbidity compared to non-pregnant women; the 

safety and immunogenicity of Tdap has not been studied in pregnant women; and the age of first infant 

dose of DTaP is six to eight weeks when maternal antibody conceivably could interfere with the infant 

response to the first two doses, critical for infant protection. Data on primary immune response to DTaP 

among infants born to vaccinated mothers is not available. Phase I studies of Tdap in pregnant women 

are planned. 

The Pertussis Workgroup administered an internal survey as the basis for drafting the recommendations. 

Of 21 respondents, 19 were in favor of gathering more evidence in one or more area before making a 

routine recommendation and two supported a routine recommendation now for Tdap in pregnant women. 

If the risk of pertussis were increased, 11 supported postpartum Tdap as soon as feasible with flexibility 

for choice by the provider. The remaining five of the 16 respondents expressed a preference for or would 

recommend Tdap during pregnancy. 

When a Td booster is due during pregnancy, 11 preferred or would recommend Td with flexibility for 

choice by the provider. The remaining five of the 16 respondents expressed a preference for or would 

recommend Tdap during pregnancy. Respondents who preferred or would recommend the Td booster 

during pregnancy favored deferring Td until delivery and administering Tdap as soon as feasible if 

sufficient Td protection was likely. The workgroup found evidence to support Td protection in most 

pregnant women. 

The 2003 National Vital Statistics showed that 97% of live births in the United States occur among 

women 11-39 years of age. A study published in 2002 with 1988-1994 NHANES data found that among 

women <40 years of age, >80% have tetanus antitoxin titers >0.15 IU/ml above the protective level of 0.1 

IU/ml and >60% of women <40 years of age had diphtheria antitoxin titers in the protective range 

(McQuillian). Although this rate is lower than for tetanus, diphtheria continues to be rare in the United 

States. Of four cases of neonatal tetanus reported in the United States since 1984, none of the mothers 

had a three-dose primary series of TT vaccine. Most women who received the ACIP recommended 

schedule of vaccination and are due for a decennial Td booster during pregnancy are likely to have 

sufficient tetanus protection until delivery. 

Dr. Murphy provided additional details on the workgroup’s deliberations in response to questions posed 

by Dr. Baker. First, safety and immunogenicity studies of Td in pregnant women were not conducted 

This document has been archived for historical purposes.
before the vaccines were licensed. Research has been performed since that time and show safety for Td 

and efficacy for protection against maternal and neonatal tetanus. 

Second, diphtheria studies have been conducted to determine potential problems with interference of 

active infant immunization, but this research did not include the current vaccine. Third, the cocoon 

approach for Tdap was only recently recommended by ACIP and has not yet been analyzed. This 

strategy has been shown to be effective in other settings, such as influenza vaccination of HCWs to 

protect elderly persons. Fourth, studies on pertussis morbidity among pregnant women are being 

conducted at this time, but CDC recognizes the interest in and need for research in this area. CDC’s 

national data do not show any pertussis deaths during pregnancy. 

Dr. Campos-Outcalt raised the possibility of using an age-specific mortality rate as a basis of comparison 

for infant pertussis deaths. Dr. Plotkin urged ACIP to develop and issue a strong statement about data on 

the safety of vaccines in pregnancy. He emphasized that an official ACIP statement would have an 

extremely positive effect on vaccine manufacturers and would also offer legal protection. 

Draft Recommendations for Tdap in Pregnant Women 

Dr. Murphy highlighted key points from four sections of the workgroup’s draft statement on the use of 

Tdap in pregnant women to facilitate ACIP’s vote and discussion. 

Introduction. Tdap is licensed for single dose use and encouraged during routine visits and before 

conception for adolescents 11-18 years and adults 19-64 years of age. Tdap replaces the next 

scheduled Td dose, protects women against pertussis, and may prevent exposure to infants who have an 

increased risk of severe and complicated disease. Pregnancy is not a contraindication for use of Tdap. 

The safety, immunogenicity and outcomes of pregnancy after Tdap administered during pregnancy are 

expected to be similar in pregnant and non-pregnant women, but these data are not available. 

High maternal titers of pertussis antibodies after Tdap during pregnancy have implications for the infant. 

Tdap might provide protection against pertussis in early life, but might also interfere with the infant’s 

ability to mount an adequate immune response to pertussis antigens in DTaP during infancy. The 

administration of Tdap may be warranted for pregnant women in certain situations. Providers who 

choose to administer Tdap during pregnancy should inform patients about the lack of data in pregnant 

women and both the potential benefits and potential adverse effect for the infant. ACIP evaluated data 

and found the evidence to be insufficient to support a recommendation for routine vaccination with Tdap 

in pregnant women at this time and is providing guidance to clinicians until more information is available. 

Section1: Routine Recommendations. Section 1A recommends Tdap for postpartum women as soon as 

feasible, but ideally before discharge from a hospital or birthing center. Breast-feeding mothers are 

included in this recommendation. Peak levels of pertussis antibodies in the mother are expected within 1-

2 weeks after vaccination. An interval of >2 years is suggested between the last Td dose and 

administration of Tdap to postpartum women. Safety of a one-time short interval since the last Td dose is 

supported by a Canadian study and is consistent with the adult Tdap recommendation, but a shorter 

interval can be used. Providers are referred to Section 2F of the statement for additional guidance. 

Section 1B outlines the dosage and route of administration for Tdap and Td. Section 1C recommends 

simultaneous vaccination with Tdap and other indicated vaccines during the same visit using separate 

syringes at different sites. Section 1D cautions providers to prevent AEs by focusing on the ageappropriate vaccine formulation and using proper technique. Section 1E informs providers that records 

are required to be maintained for vaccines covered under the National Childhood Vaccine Injury 

ACIP Meeting Minutes June 29-30, 2006 Page 53 

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ACIP Meeting Minutes June 29-30, 2006 Page 54 

Compensation Act. Adolescents and adults are also encouraged to maintain a personal vaccine record to 

prevent unnecessary immunizations. The guidance for “vaccine providers to record the type of vaccine, 

manufacturer, etc...” is now replaced with “ideally, the vaccine record will document the type of vaccine, 

manufacturer, etc.....” 

Section 2: Special Situations. Section 2A describes considerations for Tdap in pregnant women. ACIP 

recommends a Td booster for protection against Td during pregnancy, but providers may consider Tdap 

instead of Td in certain situations, such as an increased risk of pertussis, tetanus booster protection, 

wound management, and primary series vaccination. Providers who choose to administer Tdap instead 

of Td during pregnancy should inform patients about the lack of safety and immunogenicity data on Tdap 

in pregnant women; the potential for early infant protection; and unknown effects of maternal antibodies 

on the infant response to DTaP. 

The second or third trimester is preferred when Td, TT or Tdap vaccines are administered to pregnant 

women to minimize the association between the vaccine and pregnancy AEs. Providers are encouraged 

to report Tdap in pregnant women to the appropriate manufacturer’s registry regardless of the trimester of 

administration due to the current lack of data on the use of Tdap in pregnant women. 

Section 2B outlines situations with an increased risk for pertussis. Providers may substitute Tdap for Td 

during pregnancy to provide protection against pertussis in the following situations: (1) adolescents 

scheduled for routine or catch-up Tdap vaccination; (2) HCWs and child care providers in contact with 

infants <12 months of age; (3) pregnant women employed by institutions with a pertussis outbreak; and 

(4) pregnant women who reside in communities with increased pertussis activity. Providers are referred 

to Section 2A for additional guidance. 

Section 2C highlights options for protection against maternal and neonatal tetanus. ACIP recommends 

Td booster vaccination if >10 years have elapsed since the last Td dose. Providers may defer the Td 

booster until delivery and administer Tdap as soon as feasible in the immediate postpartum period if Td 

immunity is likely to be sufficient until delivery. Td immunity will most likely be adequate until delivery in 

the following groups: (1) pregnant women <30 years of age who had a childhood series of DTP or DTaP 

and at least one Td booster; (2) pregnant women >30 years of age who had a childhood series of DTP 

and at least two Td boosters; and (3) pregnant women with protective levels of serum tetanus antitoxin. 

ACIP recommends Td during pregnancy for women who will not have sufficient tetanus and diphtheria 

immunity until delivery in the following situations: (1) for protection against tetanus, (2) if traveling to a 

diphtheria endemic area, and (3) in compliance with the woman’s personal choice to have the booster 

during pregnancy. Providers may choose to substitute Tdap for Td during pregnancy to add protection 

against pertussis. Section 2D notes that a Td booster may be recommended for wound management if 

>5 years have elapsed since the previous Td dose. Providers may choose to substitute Tdap for Td 

during pregnancy. 

Section 2E addresses pregnant women with unknown or incomplete tetanus vaccination. ACIP 

recommends a three-dose primary series of Td vaccine with dose 2 given >4 weeks after dose 1 and 

dose 3 given >6 months after dose 2. Td is preferred for the first two doses that should be administered 

during pregnancy. Providers may choose to substitute Tdap for one dose of Td during pregnancy. 

Providers are referred to Section 2A for additional guidance. 

Section 2F provides information for postpartum women who received tetanus toxoid- or diphtheria toxoidcontaining vaccines <2 years previously. No studies have evaluated the risk of adverse local and 

systemic reactions at intervals <2 years since the last dose of tetanus toxoid- or diphtheria toxoidcontaining vaccine. Higher rates and more severe local systemic reactions are likely with higher serum 

titers of antitoxin. These outcomes are caused by a short interval between and an increasing number of 

This document has been archived for historical purposes.
doses. Providers may consider Tdap for these postpartum women after obtaining a history of AEs 

following previous doses. Providers are referred to the “Safety Considerations” section for additional 

guidance. 

Section 2G summarizes alternatives to Tdap in postpartum women to reduce the risk of pertussis. 

Providers should encourage vaccination of household and child care provider contacts of infants <12 

months of age. Providers are referred to the “cocoon strategy” in the Adult Tdap provisional 

recommendations for additional guidance. Providers are urged to inform patients about the symptoms of 

pertussis and the effectiveness of early antimicrobial prophylaxis. Providers are referred to CDC’s 

published guidelines in the MMWR.

Section 3: Contraindications and Precautions. Section 3A describes the contraindications for use of Td 

and Tdap: a history of serious allergic reaction to any component of the vaccine or for Tdap but not Td, a 

history of encephalopathy not attributable to an identifiable cause within seven days post-vaccination with 

pertussis components. Section 3B highlights precautions and reasons to defer Td or Tdap, namely GBS, 

with onset <6 weeks following tetanus toxoid-containing vaccine, moderate or severe acute illness until 

resolved, or a history of Arthus reaction following a previous dose. Reasons are also outlined to defer 

Tdap, but not Td: for adults 19-64 years of age, an unstable neurological condition (e.g., cerebrovascular 

event or acute encephalopathy) and for adolescents 11-18 years of age, a progressive neurological 

disorder or uncontrolled epilepsy until stable. Additional sections of the Tdap statement include guidance 

on reporting AEs after vaccination and the Vaccine Injury Compensation Act. 

ACIP Vote on the Draft Recommendations for Tdap in Pregnant Women 

Dr. Gilsdorf expressed concern about ACIP issuing a routine recommendation for the use of Tdap during 

pregnancy in the absence of solid data. She noted that the cocooning strategy for postpartum Tdap was 

successful with rubella and should be applied in this situation until better information is collected for ACIP 

to make a more informed decision. Dr. Campbell strongly recommended changing the “postpartum Tdap” 

language in Section 1A to administer the dose “prior to discharge (or as soon as feasible).” This revision 

would address the issue of women who deliver and will not present to their healthcare providers again 

until six weeks postpartum. Dr. Campbell was uncertain about the approach that would be taken to 

define a “community with increased pertussis activity” in Section 2B. 

Dr. Murphy provided additional details in response to questions posed by Dr. Campbell and Ms. 

Stinchfield. First, a “community with increased pertussis activity” is defined by local and state public 

health agencies. Second, recent FDA data showed that as of May 26, 2006, 13 cases of women who 

inadvertently received Tdap while pregnant were reported to two manufacturers’ registries. Of 12 reports 

to one manufacturer, four were from a post-marketing study and the remaining eight were spontaneous 

reports. No additional data are available. 

Dr. Baker was uncertain about the feasibility of obtaining more data in response to ACIP’s request for 

additional evidence. No safety and efficacy trials in pregnant women are underway and manufacturers 

have no incentive for conducting these types of studies. She urged CDC to gather data on the morbidity 

of pertussis in pregnant women. 

Because the workgroup is not supporting a recommendation for routine vaccination with Tdap in pregnant 

women at this time, Dr. Baker strongly encouraged CDC to disseminate data each year on the number of 

pertussis deaths among infants <4 months of age. She reported that the AAP liaison to the Pertussis 

Working Group was one of the few workgroup members who favored a routine recommendation of Tdap 

during pregnancy at this time. Due to the number of infant deaths and hospitalizations from pertussis, 

ACIP Meeting Minutes June 29-30, 2006 Page 55 

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ACIP Meeting Minutes June 29-30, 2006 Page 56 

she implored ACIP to reconsider its position. Dr. Powell announced that AAP issued a statement 

advising providers to administer Tdap to teens without concerns about pregnancy. 

Similar to Dr. Baker, Dr. Powell was also uncertain about the workgroup’s recommendation because 

pertussis morbidity and mortality are inversely related to age. He conveyed that the population in most 

need of protection from pertussis is infants prior to active immunization. This goal can be achieved 

through passive vaccination by boosting the mother. Dr. Iskander asked the workgroup to delete “second 

and third trimester” from Section 2A on “Td, TT or Tdap vaccine in pregnant women.” He explained that 

this language was extracted from ACIP’s previous influenza recommendations before the substantial 

burden of influenza morbidity was documented. 

Dr. Treanor did not see a need to collect additional safety data on the use of Tdap during pregnancy. 

Instead, he was more interested in evidence that demonstrated a tradeoff between the advantages of 

more maternal antibody and protection of young infants versus the disadvantages of suppression from 

maternal immunization. Dr. Plotkin raised the possibility of CDC and WHO gathering more data by 

conducting a study in an area of the developing world with a high rate of pertussis. The cohort could be 

pregnant women immunized with a paucivalent vaccine and the design could be utilization of antibodies 

to measure infection and disease. He pointed out that the study would be ethical in this setting so long as 

infants were followed and given a fourth dose after the Expanded Program on Immunization schedule to 

avoid harm to immunity. 

Dr. Decker described two efforts that are underway to gather more data on vaccines in pregnancy. First, 

NIH is organizing a Phase I study on third-trimester administration of Tdap in ~50 pregnant women. 

Second, New Hampshire public health agencies and sanofi pasteur are conducting comprehensive 

surveillance in response to a large pertussis outbreak that recently occurred in New Hampshire. The 

cohort includes HCWs and pregnant women who were immunized with ADACEL®

. The study is expected 

to produce a strong body of evidence on antibody responses of pregnant women, responses of infants 

and seventh-month cord blood. 

Dr. Baker provided additional details about the design of the NIH randomized Phase I trial among 45 

pregnant women 18-40 years of age. Eligibility criteria include a trisomy and alpha-fetoprotein risk 

screen. An amniocentesis will be required for all subjects with a risk >1 out of 270. Each infant will be 

bled a minimum of three times. The cohort is expected to be enrolled over a two-year period and only 30 

of 45 subjects will receive Tdap. In addition to the NIH trial and other ongoing efforts, Dr. Baker urged 

CDC to gather evidence to determine the level of interference that will result in pertussis disease to 

infants. 

Dr. Pickering urged the workgroup to incorporate language into the Tdap statement that advises providers 

about appropriate actions in the event an unlicensed rather than the licensed vaccine is administered to 

adults. He also raised the possibility of CDC making efforts at this time to prepare for a future pertussis 

outbreak. This approach would facilitate more rapid data collection on vaccines in pregnant women than 

Phase I studies. 

Dr. Murphy confirmed that CDC has taken steps in this regard by convening an expert panel to identify 

specific study design criteria for vaccine trials in pregnant women and a follow-up study of their infants. 

One possibility would be to apply criteria that FDA used to license the vaccines because FDA’s 

determination of efficacy was based on comparative bridging immunogenicity from infant trials. However, 

additional discussion is needed in this area. 

Dr. Abramson called for a motion on the draft recommendations for the use of Tdap in pregnant women. 

Dr. Morse moved as follows: “ACIP adopts the Pertussis Workgroup’s proposed recommendations, but 

will change the “postpartum Tdap” language in Section 1A to administer the dose “prior to discharge (or 

This document has been archived for historical purposes.
as soon as feasible).” The motion was seconded by Dr. Gilsdorf and passed by a majority vote. The 

disposition of the vote is as follows: 

• 14 in favor: Allos, Beck, Campbell, Finger, Gilsdorf, Hull, Lieu, Marcuse, Morita, Morse, 

Poland, Stinchfield, Treanor, Womeodu. 

• 1 opposed: Abramson. 

• 0 abstentions. 

Adult Immunization Schedule (AIS) for October 2006-September 2007 

Dr. Gregory Poland, the Adult Immunization Workgroup Chair, summarized the major changes to the 

October 2006-September 2007 AIS. A hatched bar was inserted to indicate that Tdap is a one-time 

recommendation. HPV was included with a line to illustrate the vaccine is recommended up to 26 years 

of age. The bar on varicella was revised in anticipation of the recommendation for the use of zoster 

vaccine in persons >60 years of age. A chart was added to show recommended vaccines by medical and 

other indications for consistency with the childhood immunization recommendations. The chart includes 

hatched bars for the Tdap and HPV vaccines. 

Revisions were made to six existing footnotes. Footnote 1 for tetanus, diphtheria and pertussis was 

revised to reflect recommendations for the administration of Tdap to adults <65 years of age; the use of 

Tdap and Td in pregnant women; the use of Tdap in persons with close contact to infants; and licensure 

of only one of two Tdap products for use in adults. Footnote 3 for MMR was revised to reflect new 

recommendations to administer a second dose of mumps vaccine to high-risk adults born during or after 

1957, such as HCWs, international travelers and students in post-secondary schools. The footnote was 

also revised to reflect recommendations for HCWs born before 1957. The need to strongly consider a 

routine one-dose policy and a second dose during an outbreak is emphasized. 

Footnote 4 for varicella was revised to reflect recommendations for the new definition of “immunity to 

varicella.” A routine second dose is recommended for all adults without evidence of immunity. The 

previous date of 1966 for U.S.-born persons to be considered immune to varicella was changed to 1980. 

The previously specified date of 1966 for history of varicella disease for non-U.S.-born persons to assume 

immunity was deleted. Footnote 5 for influenza was revised to reflect expanded recommendations to 

vaccinate close contacts of children 24-59 months of age. Footnote 9 for hepatitis B was revised to 

reflect recommendations to vaccinate any adult seeking protection from HepB vaccine infection. 

Footnote 10 for meningococcal was revised to reflect existing recommendations to consider revaccination after 3-5 years if the patient previously received the polysaccharide vaccine and remained at 

high risk. A new footnote was added for HPV to reflect recommendations for routine vaccination of all 

adult women through 26 years of age and delayed vaccination of pregnant women until the completion of 

the pregnancy. 

A date was added to the box on page 1 for consistency with the childhood/AIS. Text was also 

incorporated into the box to indicate zoster and other new vaccines and highlight typhoid, rabies, travel 

vaccines and other vaccines not listed on the routine AIS. The broken red line was deleted. The purple 

bars were retained are now the sole legend to highlight vaccination of persons with specific risk factors. 

Dr. Abramson called for a motion on the revised AIS. Dr. Poland moved as follows: “ACIP accepts the 

October 2006-September 2007 AIS as presented.” The motion was seconded by Dr. Finger and 

unanimously approved by all 15 voting members: Abramson, Allos, Beck, Campbell, Finger, Gilsdorf, 

Hull, Lieu, Marcuse, Morita, Morse, Poland, Stinchfield, Treanor, Womeodu. 

ACIP Meeting Minutes June 29-30, 2006 Page 57 

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Update on Pneumococcal Vaccines 

Dr. John Moran, of CDC, provided an update on the use of pneumococcal vaccines to reduce morbidity 

and mortality in an influenza pandemic. Influenza infection increases susceptibility to invasive 

pneumococcal disease (IPD). CDC formed an internal workgroup to assess the potential need for 

antibiotic stockpiles to treat bacterial complications of an influenza pandemic. The workgroup estimated 

that the proportion of pandemic influenza cases complicated by secondary bacterial pneumonia is 5%-

20% and the proportion of secondary pneumonia caused by S. pneumoniae is 50%. 

Various studies have demonstrated the effectiveness of pneumococcal vaccines against disease caused 

by vaccine serotypes. The pneumococcal conjugate vaccine (PCV7) reduces carriage and has been 

found to be >95% effective against IPD caused by vaccine serotypes and 6%-37% effective against 

pneumonia. The pneumococcal polysaccharide vaccine (PPV23) does not reduce carriage and has not 

been found to be effective against non-bacteremic pneumonia in high-risk groups. However, PPV23 has 

demonstrated efficacy of 55%-75% against IPD caused by vaccine serotypes. Data collected from the 

2004 Active Bacterial Core Surveillance Program showed the proportion of cases caused by vaccine 

serotypes. PPV23 has 23 serotypes and covers 83% of infections in adults and 83% of infections in 

children >2 years of age. PCV7 has seven serotypes and covers 24% of infections in adults and 14% of 

infections in children <9 years of age. 

Outcomes of a randomized controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV9) for the 

prevention of pneumonia were published in 2004 (Madhi, et al.). The study was conducted in South 

Africa with a vaccine that includes nine serotypes that cause 87% of IPD in South African children. An 

analysis of children hospitalized with pneumonia from whom influenza A virus was recovered found only 

170 such cases per 100,000 among vaccinated children versus 306 per 100,000 among controls; a 45% 

efficacy for preventing influenza A-associated pneumonia. The efficacy rate was found to be 34% among 

HIV-uninfected children and 57% among HIV-infected children. 

ACIP recommends that all U.S. infants receive a series of three PCV7 shots, but published data from the 

2004 NIS showed that in only 13 states had >80% of children received three shots by the age of two and 

in eight states fewer than 60% of 2-year-old children had received three shots. The median coverage 

was 71.7% in all 50 states and the District of Columbia. 

ACIP recommends that all persons >65 years of age receive PPV23, but data from the 2003 Behavioral 

Risk Factor Surveillance Survey (BRFSS) showed that one-third of older Americans are unprotected. 

Only five states had >70% coverage, three states had <60% coverage, and the median coverage was 

64.5%. ACIP also recommends PCV23 for persons 18-64 years of age with diabetes, but 2003 BRFSS 

data showed that less than one-half of diabetics have protection of PPV23. The median coverage was 

37.1% with only four states having >50% coverage and nine states having <30% coverage. These data 

indicate that existing ACIP recommendations for the prevention of pneumococcal disease by 

immunization are not fully implemented. 

Several potential options can be considered for the use of pneumococcal vaccines. Implementation of 

the current recommendations could be encouraged to increase coverage to 90% in each state. The 

current recommendations could be expanded for the use of PPV23, PCV7 or both vaccines in populations 

for whom pneumococcal vaccine is not now routinely recommended. High-risk and elderly persons could 

be regularly re-vaccinated with PPV23 (no more than two doses are currently recommended for any 

group). PCV7 could be used in older children or adults. The age for universal vaccination with PPV23 

could be lowered below 65 years. 

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ACIP Meeting Minutes June 29-30, 2006 Page 59 

If a pandemic was imminent, all persons could be considered to be “high risk” because they would be at 

increased risk of developing pneumococcal disease as a result of being at increased risk of developing 

influenza. The current recommendations could be unchanged until a pandemic was imminent and then 

changed to recommend age-appropriate pneumococcal vaccine for all persons. However, this plan would 

require stockpiling of one or both vaccines. 

CDC acknowledges that these options present several challenges. In the United States, only one 

manufacturer is licensed to produce PCV7 and only one manufacturer is licensed to produce PPV23. 

Logistical barriers to administering the vaccines during a pandemic are likely. The duration of protection 

is uncertain, particularly with PCV7. The value of continuous administration of boosters is unknown; 

individuals may become less responsive to successive re-vaccinations. Stockpiling would pose an 

additional logistical problem because PCV7 and PPV23 require constant refrigeration and have limited 

shelf lives. 

Strategies to prioritize populations have not been identified to date, such as by age group or persons 

most likely to develop influenza or pneumococcal disease. For example, IPD is most common among 

very young and very old persons with the lowest attack rate in 2005 at 5-17 years of age. However, the 

highest attack rates for influenza during the 1918 and 1957 pandemics were among persons 5-19 years 

of age. Dr. Moran asked ACIP members for their thoughts on how the currently licensed pneumococcal 

vaccines might be used for influenza preparedness. 

Dr. Hull raised the possibility of CDC combining attack rate data for both influenza and pneumococcal 

disease to calculate an overall risk profile. He also responded to CDC’s question of whether each state 

would consider using its individual pandemic influenza resources to increase pneumococcal vaccine 

coverage. He explained that states would need to address this issue in the context of a comprehensive 

preparedness program rather than a stand-alone activity. As a result, states must consider the additional 

resources and extra burden required to undertake this effort. 

Ms. Stinchfield asked CDC to consider HCWs in pandemic preparedness if a decision is made to expand 

the current target groups. Dr. Womeodu encouraged CDC to include nursing homes and other facilities 

that house elderly persons in pandemic influenza planning. She requested that an explicit process be 

developed to retain and care for elderly persons in existing facilities rather than transferring these 

individuals to an emergency department during an influenza pandemic. Dr. Treanor acknowledged the 

need for CDC to clearly distinguish between improving coverage in existing target groups recommended 

for pneumococcal vaccine and increasing vaccine use in non-traditional target populations during a 

pandemic. 

Dr. Morse was in favor of lowering the age of universal vaccination with PPV23 to < 65 years rather than 

stockpiling vaccine. Dr. Wallace conveyed that three PCV7 doses do not necessarily correlate with the 

current estimates for protection because these data are based on previous supply issues, vaccine 

shortages and catch-up vaccination. In response to Dr. Poland’s question, Dr. Moran clarified that the 

Haemophilus vaccine would most likely be unimportant during a pandemic due to the dramatic decrease 

in Haemophilus influenzae B (Hib) disease covered by this vaccine. 

Dr. Whitley-Williams, the National Medical Association liaison, urged CDC to consider the significant gaps 

in both pneumococcal and influenza vaccine coverage among minority adult populations; make efforts to 

narrow these gaps during pandemic planning; and identify resources to increase pneumococcal vaccine 

coverage. Dr. Moran confirmed that CDC would continue its internal discussions on the possibility of 

using PPV23 to reduce gaps in incidence between whites and minority populations. 

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Dr. Litjen Tan, the American Medical Association (AMA) liaison, urged ACIP to continue its dialogue on 

using pneumococcal vaccines to reduce morbidity and mortality in an influenza pandemic. AMA recently 

distributed a pamphlet to 350,000 members describing actions physicians can take in their individual 

practices with respect to pandemic planning. The pamphlet reiterated and encouraged implementation of 

ACIP’s existing recommendations on PPV23. Dr. Tan asked ACIP to explore the possibility of issuing 

new guidance on pneumococcal vaccines. Ms. Kelly Moore, of the Tennessee Department of Health, 

suggested using the strong community-level interest in influenza pandemic planning to increase vaccine 

coverage and link pneumococcal vaccines to pandemic planning and preparedness. 

Several manufacturers responded to Dr. Abramson’s questions about the actual shelf lives of 

pneumococcal vaccines and current efforts to develop additional conjugate vaccines with more strains. 

Dr. Jeffrey Silber, of Merck, clarified that the shelf life of a vaccine is based on the stability of serotypes. 

For example, PPV23 is actually 23 different vaccines in one vial and could essentially have 23 different 

shelf lives. Dr. Andrew MacKnight announced that GSK is currently making progress on Phase III studies 

of a 10-valent pneumococcal vaccine. 

Dr. Peter Paradiso, the liaison for Pharmaceutical Research and Manufacturers of America, announced 

that other countries are adopting PCV7 due to the high coverage rate of the vaccine and the tremendous 

reduction in pneumococcal disease. He also informed ACIP that Wyeth Vaccines is developing a 13-

valent vaccine with increased coverage of serotypes 6A and 19A. The new vaccine has the potential to 

play a critical role in antibiotic resistance and the use of a conjugate vaccine in adults. Wyeth is currently 

collaborating with FDA to design the overall program for the vaccine and will initiate the Phase III trial of 

the 13-valent vaccine in the near future. Dr. Paradiso confirmed that Prevnar has a 2-year shelf life in the 

bottle. 

Dr. Abramson closed the discussion by announcing that key ACIP members and CDC staff would engage 

in dialogue to determine the need to form a new Pneumococcal Workgroup. 

HERPES ZOSTER (HZ/SHINGLES) VACCINE 

The series of presentations and ACIP’s discussion on the HZ/shingles vaccine are set forth below. 

Evaluation of the Vaccine Cost-Effectiveness 

Dr. James Pellissier, of Merck Research Laboratories, presented Merck’s cost-effectiveness evaluation of 

ZOSTAVAX®

 in preventing zoster and post-herpetic neuralgia (PHN) in older adults in the United States. 

Merck used several data sources to demonstrate the safety and efficacy of ZOSTAVAX®

 and its costeffective price of $150 in immunocompetent persons and other individuals >60 years of age. These data 

were also used to support recommendations of ZOSTAVAX®

 and show that the vaccine is comparable to 

other adult preventative measures. The data sources included the pivotal Shingles Prevention Study 

(SPS), commonly accepted cost-effectiveness thresholds, and sensitivity analyses with a variety of 

decision-making thresholds for cost-effectiveness. Merck designed the cost-effectiveness evaluation with 

conservative analyses, robust conclusions, plausible ranges of input parameter values, and a broad 

scope of scenarios and age cohorts. 

HZ and PHN are debilitating diseases that have an unmet medical need for better management. HZ 

occurs through the reactivation of latent VZV. The disease is typically characterized by prodromal pain 

and an acute rash accompanied by moderate to severe pain. The lifetime risk of developing HZ is 

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ACIP Meeting Minutes June 29-30, 2006 Page 61 

approximately 30%, but up to ~50% of persons >85 years of age will develop >1 HZ episodes. HZ 

complications occur in 15%-40% of cases with PHN being the most common complication. Depending on 

age, 10%-33% of all HZ cases lead to PHN. The overwhelming burden associated with HZ and PHN is 

borne by the elderly. For purposes of the cost-effectiveness evaluation, Merck used the SPS definition of 

PHN as “persistent pain >90 days after the onset of HZ.” 

The SPS was a large, randomized and double-blind placebo controlled clinical trial that showed the 

ZOSTAVAX®

 live attenuated VZV vaccine to be generally well-tolerated and efficacious in subjects >60 

years of age. Key SPS results on ZOSTAVAX®

 are highlighted as follows. HZ incidence was reduced 

with vaccine efficacy of 51%. The proportion of PHN cases was decreased with vaccine efficacy of 47% 

among subjects >70 years of age who were given HZ. The incidence of PHN in the overall cohort was 

reduced with vaccine efficacy of 67%. The safety profile was found to be excellent. 

Merck conducted research to gain insight into the potential value of ZOSTAVAX®

 to society and payers. 

The payer perspective addressed direct medical costs, while the societal perspective included direct 

medical costs, lost work and productivity, and other indirect costs. The study was designed with a modelbased decision analysis to estimate expected HZ, PHN and complications avoided; health care resource 

utilization (HCRU) costs avoided; QALYs gained; and the cost-effectiveness or marginal cost per QALY 

gained. A cohort-based and age-specific model published in 2001 served as the foundation for the Merck 

model (Edmunds, et al.). Merck designed the model to accommodate inputs from the SPS, literature, 

ancillary studies, and the existing HZ and PHN knowledge base. The model provided lifetime projections 

of HZ, PHN, healthcare resource use and QALYs. 

The six categories of data that were input into the Merck core model are described as follows. One, 

vaccine characteristics included vaccine efficacy for HZ and PHN, price and durability of the vaccine 

effect. Two, epidemiologic data included age-specific HZ-related death rates and HZ/PHN incidence, life 

expectancy, duration of HZ/PHN cases, and the rate of zoster-related complications. Three, HCRU and 

cost data included outpatient and emergency room visits, hospitalizations, prescription fills, and other 

healthcare factors, such as home care, tests and procedures. Four, quality of life data included QALY 

weights for HZ-associated pain states and duration of pain by severity. Five, indirect cost data included 

work and productivity losses attributable to HZ, PHN or related complications, age-specific employment 

rates, and wage rates. Six, other parameters included the cohort size, vaccine recipient population, and 

the 3% discount rate for costs and outcomes. 

Merck took several actions to model the long-term efficacy of ZOSTAVAX®

. Vaccine efficacy results were 

extracted from the SPS and analyzed by age of vaccination. A maximum likelihood was estimated to 

identify the best fitting age-dependent models. Fitted results of the model indicated a reduction in efficacy 

by age, a 0% waning rate, and an average duration of efficacy of >12 years. The large MedStat insurer 

database served as the source for epidemiologic and HCRU data. The data showed much higher 

incidence rates for immunocompromised persons compared to immunocompetent persons, but 

ZOSTAVAX®

 will only be indicated for immunocompetent persons. Merck accounted for this potential 

flaw by conducting analyses with data from all individuals and immunocompetent persons to bind results. 

Key results from Merck’s cost-effectiveness evaluation of ZOSTAVAX®

 are summarized as follows. 

Model costs ranged from $437-$4,818 for acute HZ, PHN, and ocular, neurological, skin and other 

complications. QALY weights were assigned for non-pain QALYs and mild, moderate and severe HZ 

pain based on weights from the literature, Merck’s base case QALY weight and SPS data. All HZ data 

and immunocompetent data were used to project the lifetime impact of ZOSTAVAX®

 on a cohort of 1 

million vaccine recipients >60 years of age. The estimates were based on avoiding HZ and PHN cases, 

related complications, HZ-related deaths, hospitalizations, emergency room and outpatient visits, and 

prescriptions. The number of these outcomes avoided ranged from 35-438,998; the number of QALYs 

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ACIP Meeting Minutes June 29-30, 2006 Page 62 

gained ranged from 4,169-6,706; and the overall costs of HZ, PHN and complication cases avoided 

ranged from ~$74-~$93 million. 

Based on a total price of $168 for the vaccine and an administrative fee, the projected cost-effectiveness 

of ZOSTAVAX®

 for the U.S. population >60 years of age ranged from $15,390-$22,474 from the payer 

perspective and $14,450-$21,524 from the societal perspective. A cost per QALY gained of $50,000 is 

frequently cited as the threshold, but cost-effectiveness indicators typically vary among decision-makers. 

However, studies published in 2005 and 2006 showed that costs per QALY gained for other adult 

preventive measures ranged from $10,000-$60,000 (Neumann and Turner, respectively). The 

interventions analyzed in these studies included hypertension medication, influenza vaccination, 

cholesterol management, and osteoporosis, mammographic and colon cancer screening. 

Merck also compared the ZOSTAVAX®

 cost-effectiveness results to a recent assessment conducted by 

the National Commission on Preventive Practices (NCPP) on the value of 25 preventive services 

recommended by ACIP and the U.S. Preventive Services Task Force. The NCPP study used a scale of 

1-5 to score each preventive service based on its clinically preventable burden and cost-effectiveness. Of 

25 services evaluated, only 11 received scores of >7. ZOSTAVAX®

 would have received a score of 7 if 

the vaccine’s cost-effectiveness and number of QALYs saved were entered into the NCPP model. The 

ZOSTAVAX®

 result is comparable to the cervical cancer and cholesterol screening scores. Merck also 

analyzed the cost-effectiveness of ZOSTAVAX®

 for persons in age groups other than >60 years. The 

data showed extremely reasonable cost-effectiveness ratios for persons up to the 85-90 year age range. 

Merck performed sensitivity analyses of the vaccine’s waning rates and probabilistic sensitivity analyses 

to determine the durability of ZOSTAVAX®

 and robustness of the overall results. Each input parameter 

was simultaneously varied across the respective ranges according to assigned probability distributions. 

The sensitivity analyses showed that ZOSTAVAX®

 was cost-effective even when durability of only five 

years was assumed. The probabilistic sensitivity analyses demonstrated that ZOSTAVAX®

 would most 

likely be cost-effective at much lower decision-making thresholds. However, the model was found to be 

sensitive to the vaccine price, age of the vaccine recipient, PHN costs, duration of vaccine efficacy, QALY 

losses associated with pain states, and complication costs. 

In addition to the sensitivity of the model, Merck also recognized that several caveats created biases 

either in favor of or against ZOSTAVAX®

. For example, complication costs covered all HZ patients with 

complications. No distinction was made between all individuals and immunocompetent persons. Costs 

for several important variables were excluded from the model, such as medication costs, QALYs lost to 

complications, costs related to care givers and care giver burden, and work and productivity costs for 

persons >65 years of age. Moreover, PHN costs were only included up to one year, but these cases may 

have a much longer duration. Costs per HZ case did not vary by case severity. Efforts are underway at 

Merck to address these caveats in the model. 

Dr. Pellissier provided additional details on Merck’s cost-effectiveness study of ZOSTAVAX®

 in response 

to ACIP’s questions. 

• Results from the probabilistic sensitivity analysis differed from other analyses because 

each input parameter varied by its input distribution. The expected value could be lower 

or higher than the probability of 50% depending on the distribution of the outcome. 

• Long-term vaccine efficacy was modeled by analyzing the take, initial efficacy and 

waning of the vaccine. Various functional forms for the fitting process were examined 

and SPS data for all ages were used. Efficacy data for years 1-5 were applied and 

maximum likelihood estimation models were fit. The efficacy level across years 1-5 for 

the age of vaccine was flat, but Merck acknowledges the weakened ability to trust 

forecasts >30 years in the future. 

This document has been archived for historical purposes.
• Merck fitted a waning parameter in the model due to the expectation of waning. The data 

set used in the study showed that the waning rate would be the same regardless of age. 

The results should be interpreted based on the sensitivity analysis because these data 

cover the entire spectrum. Extremely reasonable results were still seen even with a 

pessimistic assumption of only an average durability of five years. 

• The probability of complications was ~10% in general based on the likelihood of having a 

complication in one of four categories: ocular, neurologic, skin or other complications. 

These complications were weighted by the observed proportion in the Olmsted County, 

Minnesota study. None of the biases observed in favor of or against ZOSTAVAX®

overwhelmed the other biases. 

Drs. Abramson and Lieu responded to a question posed by Dr. Andrea Gelzer, the liaison to America’s 

Health Insurance Plan. The ACIP members are currently exploring strategies to standardize costeffectiveness data presented to ACIP. However, a balance must be made between standardizing 

information and acknowledging differences between desired outcomes of vaccines, such as decreased 

pain, morbidity or mortality. Dr. Lieu welcomed the opportunity to further address this issue with the 

liaisons pending the results of ACIP’s discussion. 

Dr. Neuzil pointed out that the ZOSTAVAX®

 cohort will be followed for efficacy over a longer period of 

time and will be >7 years ahead of any population immunized with a licensed vaccine. She emphasized 

that knowledge gained about the duration of protection can be incorporated into the models to resolve 

uncertainties at the time the vaccine is licensed. 

Projected Cost-Effectiveness of Vaccinating the Elderly to Prevent Shingles 

Dr. Ismael Ortega-Sanchez, of CDC, presented preliminary data from CDC’s cost-effectiveness study of 

vaccinating elderly persons in the United States to prevent shingles. Death is an extremely rare outcome 

of shingles, but severe pain and suffering are a significant burden of the disease. A new vaccine in 

immunocompetent elderly persons has been shown to markedly reduce the burden of illness from 

shingles and PHN. CDC designed its study to identify the value of preventing a case of shingles from a 

payer and societal perspective and determine whether vaccination of the elderly to prevent shingles 

would provide a public health value. 

CDC’s cohort-based decision analysis model for the study was age-specific and based on the current 

U.S. population. The model incorporated assumed probability distributions, focused on an 

immunocompetent population, used a Monte Carlo simulation algorithm to estimate results, and projected 

health economic outcomes from 60-99 years of age. The six major categories of data included in the 

model were epidemiologic data, quality of life and vaccine efficacy data, HCRU data and cost parameters. 

With these data, the model estimated HZ prevention parameters, cases of shingles and PHN prevented, 

burden prevented, and cost-effectiveness ratios. 

Because shingles causes impairment and disability that in turn leads to a lower quality of life, most of the 

expected benefits from prevented reactivation of HZ virus (shingles) are in terms of reductions in 

morbidity and prevention of quality of life losses. The primary outcomes measured in the study were 

QALYs and costs per QALY gained. QALYs gained measure years of life saved, years of function and 

health preserved. The cost utility analyses included changes in quality of life as a key outcome. The 

secondary outcomes measured in the study were the number of vaccinees to avert one case of shingles 

and PHN and the cost per outcome averted for the cost of each shingles and PHN case. 

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The CDC model used various sources to collect data for the model, including the published literature, 

MedStat, the U.S. Census Bureau, the Zoster Utility Evaluation (ZUE) study, and the Bureau of Labor 

Statistics (BLS). These sources were used to gather epidemiologic data, cost estimates, vaccine efficacy 

data, hourly and lifetime earnings, age-specific incidence of shingles, and data on the U.S. population and 

impact of disease on quality of life due to pain and suffering. 

The ZUE study was an extremely important data source for CDC’s cost-effectiveness analysis of shingles 

vaccination. The joint research project between CDC and Harvard measured the economic value of 

preventing zoster by assessing medical and non-medical care use; evaluating the patient’s monetary and 

indirect costs; and estimating intangible values of prevention in standard shingles scenarios with a time 

tradeoff technique. In the ZUE study, “intangible values of prevention” were defined as the amount of 

time in perfect health at the end of life an individual would be willing to trade to avoid, for example, a 

month with a certain level of pain and complication due to shingles. 

The ZUE study population included two groups. Patients with recent shingles or PHN were recruited from 

two sites and interviewed by telephone. Community members were selected to be representative of the 

U.S. general population in terms of race, ethnicity and socioeconomic status. This group completed webbased self-administered surveys. The public cohort had significantly more conservative scores for level 

and duration of pain than the patient cohort (e.g., public preferences express lesser decrements in quality 

of life than those of patients). 

Analyses in the CDC cost-utility model were conducted using the patient and public perspectives 

regarding the impact in the quality of life under different scenarios of pain intensity and duration. CDC 

also used ZUE and MedStat data on medical and non-medical resource use; cost by shingles case; and 

cost per case with and without persistent pain for 30-89 days and >90 days. CDC used these data 

sources to analyze several outcomes, such as use of inpatient or outpatient services; length of 

hospitalization; work and leisure time lost, time spent by other care givers; other out-of-pocket expenses; 

and number of prescriptions, medical visits or encounters, emergency department or doctor visits and 

telephone calls for advice. 

CDC designed the model based on several assumptions; most are standard cost-effectiveness 

assumptions. Among the specific shingles and PHN assumptions made for this study, CDC had that the 

reactivation recurrence would be 1%-1.5% after five years. The proportion of immunocompetent persons 

would be age-specific with a mean of 90% among persons >60 years of age. The baseline health status 

would be age-specific with a mean of 0.86 among persons >60 years of age using quality adjustment 

weights. Duration of vaccine efficacy would be age-specific. Vaccine local reactions and fever would be 

31% and 1.4%, respectively, among vaccinees. Vaccine administration would cost $20 with a range of 

$15-$50. The discount rate for all costs and health outcomes would be 3% with a range of 0%-5%. 

The preliminary results of CDC’s cost-effectiveness analysis are summarized as follows. If after five 

years, 68% of vaccine efficacy remains, vaccination of 1 million persons would prevent 58,000 shingles 

cases, 7,000 complications, 32,000 PHN cases with pain >30 days, and five deaths. The number of 

vaccinees needed would be 17 to prevent one shingles cases, 143 to prevent one complication, 31 to 

prevent one PHN case, and 194,000 to prevent one death. Vaccination of 1 million persons >60 years of 

age would prevent 285,000 ambulatory visits, 28,000 emergency department visits, 6,000 days of 

hospitalizations, 176,000 prescriptions, 700,000 lost work hours, and 4 million lost hours for other 

activities. Shingles costs saved before vaccination would be ~$49 million. Using the patient perspective 

on QALY scores, the number of QALYs gained with vaccination would be 11,919 non-discounted and 

8,782 discounted. Overall, shingles vaccination would prevent 43% of medical and non-medical 

resources. 

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ACIP Meeting Minutes June 29-30, 2006 Page 65 

CDC performed several sensitivity analyses to determine the number of PHN cases prevented per 1 

million persons >60 years of age; the cost per QALY saved by score perspective and vaccine 

effectiveness; and the cost per QALY saved by vaccine price for three vaccine efficacy duration 

scenarios. The sensitivity analyses showed that QALYs and cost per QALY gained were highly sensitive 

to the vaccine cost, QALY scores perspective, vaccine effectiveness for PHN and duration of vaccineinduced protection. 

CDC acknowledges both the strengths and weaknesses of the study. On the one hand, healthcare 

utilization, out-of-pocket expenses and productivity losses were captured from actual patients. Data on 

quality of life changes from shingles were extracted from a large sample size with solid response rates 

and diverse healthcare and geographic settings. QALY scores were estimated with a parallel comparison 

between patients and community controls. The survey questions asked patients to provide responses on 

hypothetical scenarios and their actual illness. 

On the other hand, indirect increments of healthcare utilization by patients with persistent pain were not 

assessed. Medical cost ascertainment to cases by level of pain and duration was limited. The scores 

were inconsistent because patients placed both high and low values on PHN. No clear distinction was 

made between extreme opinions and response errors. Questions on time compensation were modified, 

particularly those related to time traded from the end of life. Overall, CDC’s preliminary data from the 

analyses demonstrated that a shingles vaccination program could be cost-effective for a cohort of 

immunocompetent persons >60 years of age. The conservative analyses did not consider indirect costs 

for PHN and immunocompromised cases. 

Dr. Ortega-Sanchez provided additional details on CDC’s preliminary cost-effectiveness study of shingles 

vaccination of elderly persons in response to ACIP’s questions. 

• CDC gathered data on the dollar amount persons would be willing to pay for the shingles 

vaccine or to avoid pain, but this information is still being analyzed. CDC will use these 

data to develop a cost-benefit analysis and expects to present this component of the 

study during the next ACIP meeting. 

• The patient cohort and community controls were well matched by age in the ZUE study, 

but not educational level. 

• CDC did not use incidence data for shingles or PHN from the SPS control group. 

Instead, CDC used the following data sources to estimate age-specific incidence of 

shingles: U.S. data by Donahue from 1990-1992; U.S. data from the MedStat database 

from 1993-2003; U.S. data from Olmsted County in 2005; and U.K. data by HopeSimpson from 1947-1962. These data sources were based on conservative estimates. 

• CDC incorporated BLS data into the model to estimate hourly wages for specific age 

groups. The data showed that persons in the indicated age group for shingles 

vaccination would earn ~$18/hour. However, CDC’s economic analysis did not include 

an hourly rate for leisure time. 

Dr. Pellissier noted that Merck also did not use incidence data for shingles or PHN from the SPS control 

group. He clarified that telephone reminders, refrigerator magnets and other methods were used to 

educate the SPS cohort on ascertainment of shingles. Utilization of SPS incidence data would have 

strongly biased the Merck study in favor of the vaccine. As a result, Merck estimated shingles incidence 

for its economic model based on the cost of care. 

Dr. Abramson announced that Medicare Part D will cover 75% of the cost of the shingles vaccine 

excluding the administrative charge. More information on this issue will be presenting during the October 

2006 ACIP meeting. Dr. Neuzil was uncertain of CDC’s rationale in solely focusing on the efficacy of the 

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vaccine against shingles. Solid data that demonstrate the efficacy of the vaccine against both PHN and 

shingles would strengthen CDC’s cost-effectiveness models. 

Dr. Patrick Liedtka, of the Merck Vaccine Division, highlighted key points from Merck’s discussions with 

CMS, Medicare Part D plans and private managed care plans over the past year. Out-of-pocket costs for 

ZOSTAVAX®

 are not anticipated to be more significant than those for other vaccines. Of the total target 

population of persons >60 years, >90% is expected to have extremely robust healthcare coverage of 

ZOSTAVAX®

. Several large managed care plans in the country have already decided to cover the 

vaccine with no co-payment to enrollees in the indicated group. 

Dr. Jeffrey Koplan, of Emory University, advised CDC to attribute a dollar figure to leisure time because 

older persons in the indicated age group for shingles vaccination may place a higher value on leisure time 

lost than work time lost. He also asked ACIP to consider the actual uses of cost-effectiveness analyses. 

Although these data are used to assist in developing healthcare and medical prevention policies, the 

information can also be used to establish and justify the price of vaccines. Dr. Koplan encouraged CDC 

to perform a sensitivity analysis to determine cost-effectiveness using a worst-case scenario for each 

variable of the vaccine. Dr. Ortega-Sanchez confirmed that CDC incorporated a Monte Carlo simulation 

algorithm into the model to obtain ranges of specific values probability distributions. 

Overview of the ZOSTAVAX® Storage, Handling and RMP 

Drs. Joan Benson and Adrian Dana, of Merck, described Merck’s plans to educate healthcare providers 

on properly storing, handling and administering ZOSTAVAX®

. Merck will apply its solid experience and 

lessons learned with frozen vaccines to ZOSTAVAX®

, but will also implement unique strategies in these 

efforts. ZOSTAVAX®

 will be administered by internists, but this provider population typically has less 

experience with immunization than pediatricians. Merck will continue its ongoing discussions with the 

Shingles Workgroup and CDC to further refine the plans. 

The following storage and administration requirements will be printed on the package. ZOSTAVAX®

should be stored frozen at an average temperature of –15°C or colder until reconstituted for injection. 

The vaccine should be immediately administered after reconstitution to minimize loss of potency. Merck 

will use its three existing general educational activities on the storage and handling of adult vaccines for 

ZOSTAVAX®

. First, the “Ready Set Vaccinate” provider education module will provide information to 

physician offices on storage, handling and all other aspects of immunization services. Second, live web 

cast educational programs will be aired on delivering safe and effective immunization services. Third, 

well-trained sales representatives will deliver information to physician offices on maintaining a vaccine 

storage temperature control log. 

Specifically for ZOSTAVAX®

, Merck will provide education to physician offices with appropriate freezer 

storage capabilities upon FDA approval of the vaccine. Physician offices without adequate freezer 

storage capabilities will be informed of alternate vaccination sites with capacity to store, handle and 

administer ZOSTAVAX®

. Support services will be provided to physicians and office staff who request 

additional information. Merck administered a survey to 27,936 internist and family physician offices to 

determine existing freezer storage capabilities. Of all respondents, 59% had appropriate freezers and 

29% had inappropriate freezers. For purposes of storing ZOSTAVAX®

, a “freezer” is defined as having a 

separate door. 

For physician offices with adequate storage and handling capabilities, sales representatives will request 

restocking of ZOSTAVAX®

. Resources will be delivered to educate these offices in properly storing and 

handling the vaccine. For physician offices without adequate storage and handling capabilities, sales 

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ACIP Meeting Minutes June 29-30, 2006 Page 67 

representatives will continue to reinforce the importance of adult vaccination. These offices will be 

informed of alternate vaccination locations to refer patients who are interested in receiving ZOSTAVAX®

. 

Merck will conduct medical education forums to educate providers on the ZOSTAVAX®

 product label and 

proper vaccine storage and handling. All physician offices that stock and administer ZOSTAVAX®

 will be 

given educational resources, including storage and handling guides, office reference materials, quick 

reference freezer door magnets, and inserts to the “Ready Set Vaccinate” education module. The 

distribution packaging for ZOSTAVAX®

 will prominently display warnings of frozen vaccine in the package 

that should be placed in the freezer immediately upon receipt. Storage instructions in each package will 

be required to be handled before the vaccine storage compartment is opened. 

Providers will be informed about their ability to immediately obtain assistance and resolve concerns 

related to any Merck vaccine through the Merck National Service Center. Customer service 

representatives will be available during business hours and will also have an FDA-approved algorithm 

that can accurately assess the viability of frozen vaccines where the cold chain has been broken. 

Providers will also be made aware of their ability to return a Merck product that has expired or was 

damaged upon receipt. 

The ZOSTAVAX®

 RMP will augment safety data from clinical trials of 21,000 adults and will include the 

following components. Merck’s passive surveillance system will be used to provide routine safety 

monitoring. The Varicella-Zoster Virus Identification Program will be expanded to include reports and 

clinical specimens from physicians of zoster-like or varicella-like rashes temporally associated with the 

vaccine; potential transmission of the vaccine virus to contacts; potential central nervous system events in 

temporal association with the vaccine; and inadvertent exposure to or vaccination of 

immunocompromised persons. The existing pregnancy registry will be expanded to include ZOSTAVAX®

. 

Studies will be conducted to address ZOSTAVAX®

’s duration of protection and concomitant use with 

other routine adult vaccines, including pneumococcal polysaccharide and tetanus-containing vaccines. 

Post-marketing safety studies will be launched to obtain additional safety data. 

The SPS will be expanded to collect persistence of efficacy data from ~7,000 vaccine recipients through 

an additional 4-6 years for a total of ten years post-vaccination. Merck completed the study on 

concomitant use with ZOSTAVAX®

 and the influenza vaccine and is currently analyzing the data. Several 

post-marketing studies are planned for ZOSTAVAX®

. A placebo-controlled general safety study will 

compare serious AEs between 6,000 ZOSTAVAX®

 subjects and 6,000 placebo subjects. A large-scale 

observational study will analyze 20,000 vaccinated subjects in an MCO setting to gain additional 

knowledge on the safety of the vaccine in routine clinical practice. A high-dose observational study will 

analyze 5,000 subjects to obtain more information on the safety and potency of ZOSTAVAX®

 at higher 

doses. A randomized, placebo-controlled and double-blind study will assess the safety of ZOSTAVAX®

among 300 subjects receiving low to moderate maintenance doses of corticosteroids. 

Drs. Benson and Dana were pleased to announce the filing of Merck’s refrigerator formulation for 

ZOSTAVAX®

, but the timeline to approve this vaccine is unknown at this point. Overall, Merck will use its 

comprehensive RMP to follow the safety of ZOSTAVAX®

. Merck will continue its strong commitment to 

increase and improve delivery and access to adult vaccines. 

Drs. Benson and Dana provided additional details about the ZOSTAVAX®

 storage, handling and RMP in 

response to ACIP’s questions. 

• Merck has made strong efforts to distinguish clearly between its varicella-containing 

vaccines. The ZOSTAVAX®

 and VARIVAX caps have different colors. The commercial 

and generic names begin with “zoster” for ZOSTAVAX®

 and “varicella” for VARIVAX. 

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However, efforts are underway at Merck to make the products even more distinct in the 

future. 

• Merck develops periodic safety update reports every six months for all its vaccines to 

analyze problems related to confusion with the product, deliveries of inaccurate vaccines 

and other issues. 

• The alternate vaccination sites will serve as a referral source for physician offices without 

adequate storage and handling capabilities or practices with no interest in administering 

ZOSTAVAX®

. The sites include pharmacy chains and vaccine service providers who 

have indicated an interest in participating in the program. The sites will be encouraged to 

complete and return a notification of vaccination letter to the referring physician to ensure 

a record is maintained. 

Considerations for Shingles Vaccine Recommendations in the United States 

Dr. Rafael Harpaz, of CDC, reported that the Shingles Workgroup reviewed data on the burden and 

epidemiology of shingles and PHN, results of the SPS, and cost-effectiveness data to draft 

recommendations on shingles vaccination in the United States. Shingles is a reactivation of VZV that 

occurs decades after initial chickenpox and leads to a crop of blisters in the dermatomal distribution. 

Excruciating pain is nearly a universal component of shingles. PHN is the key sequela of shingles and is 

an incapacitating and prolonged condition that can last up to years. The effectiveness of PHN prevention 

and treatment is partial and inconsistent. 

The risk of shingles increases ten-fold with age with annual rates of ~0.1% in children and ~1% in elderly 

persons. The risk of shingles progressing to PHN with pain lasting >90 days from rash increases threefold with age. The progression from shingles to PHN is 6% in young adults and 20% in elderly persons. 

Immunosuppression is less common, but is still a high risk factor for shingles. However, the live 

attenuated ZOSTAVAX®

 vaccine is not licensed for immunosuppressed persons. The incidence of 

shingles and PHN in the United States is ~4/1,000 per year or ~1 million cases annually. The lifetime risk 

of developing HZ is 25%-30% with 100,000-200,000 new PHN cases occurring annually. 

The pivotal SPS included >38,000 enrollees and demonstrated overall vaccine efficacy of 51% for HZ and 

67% for PHN. However, vaccine efficacy for HZ and PHN ranged from 18%-74% depending on different 

age groups of 60-69 years, 70-79 years and >80 years. The SPS showed that vaccine efficacy for HZ 

and PHN declined in year 1, but remained stable through 48 months of follow-up. A protective effect was 

seen in persons who developed shingles despite vaccination history. The slight excess in serious AEs 

observed in a sub-study was not seen in the full SPS population and did not indicate causality due to a 

temporal or organ system pattern. Overall, the SPS found the vaccine to be safe. 

The catalog price of ZOSTAX is $150 for a one-dose regimen. Merck’s cost-effective analysis showed 

that the vaccine would be cost-effective from both a societal and payer’s perspective at an average cost 

of $19,487 per QALY. For prevention purposes, ~22 persons would need to be vaccinated to prevent one 

shingles case and 65-100 persons would need to be vaccinated to prevent one PHN case. CDC’s costeffective analysis showed that the vaccine would be cost-effective from a societal perspective at a cost of 

$14,800-$34,900 per QALY. For prevention purposes, 17 persons would need to be vaccinated to 

prevent one shingles case and 31 persons would need to be vaccinated to prevent one PHN case. The 

cost per shingles and PHN cases prevented was $3,300 and $6,400, respectively. 

The Shingles Workgroup has not reached consensus on the three draft recommendations at this time 

because the CDC and Merck cost-effectiveness analyses and data from the package insert were only 

recently presented. However, the workgroup is now soliciting ACIP’s input on these issues. One, the 

ACIP Meeting Minutes June 29-30, 2006 Page 68 

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ACIP Meeting Minutes June 29-30, 2006 Page 69 

workgroup’s consensus opinion on whether ACIP should recommend universal or permissive shingles 

vaccination for persons >60 years of age is pending additional cost analysis data from CDC and Merck. 

However, the majority of members support a universal recommendation. 

The workgroup is considering several issues to decide on a universal versus permissive recommendation. 

The burden of disease is substantial. The vaccine is safe and moderately effective. Survey data show 

interest by patients and providers. Preliminary results demonstrate that the vaccine is cost-effective from 

a societal perspective, but the workgroup acknowledged the evolving nature of economic tools to value 

pain and the sensitivity of these tools to assumptions. The main burden of pain is borne by the individual 

rather than the payer or society. Shingles is not contagious. Lost productivity and severe disease or 

death are likely to be less important to retirees and immunocompetent persons. However, PHN may be 

worse than death in extreme cases. Vaccine financing by Medicare, VA and private insurers will depend 

on the nature of ACIP’s recommendation. Permissive language may reduce overall access and lead to 

social disparities. 

Two, the workgroup is divided at this time on whether ACIP should extend guidance on shingles 

vaccination to persons 50-59 years of age beyond the package label. The majority of members 

supported no guidance for cohorts outside the package label. A minority of members were in favor of 

considering vaccination for this age group and highlighting the physician prerogative. No members 

expressed an interest in recommending shingles vaccination for persons 50-59 years of age at this time. 

The workgroup is considering several issues to decide on these three options. The vaccine is not 

licensed for persons 50-59 years of age. ACIP has no history in making off-label recommendations for 

large cohorts. This guidance would establish a precedent and would also have broad implications for 

future ACIP recommendations. Physicians currently have the prerogative to vaccinate off-label, but 

specific language from ACIP may change practices. Persons 50-59 years of age have less pain with 

shingles than those in older age groups, but the burden of disease is still substantial and accounts for lost 

work productivity in this large population. No efficacy data have been produced to date on shingles 

vaccination in this population. 

The SPS Phase III study demonstrated the plausibility of vaccine efficacy in subjects >60 years of age, 

but the data also showed that efficacy was highest in the youngest age strata. However, immunogenicity 

studies on persons 50-59 years of age included a minimal number of subjects and imperfect correlates of 

protection. Cost-effectiveness of vaccination in this population from a societal perspective is still 

unknown. Surveys indicate fair interest by providers of vaccination for persons 50-59 years of age. 

Three, the workgroup is divided at this time on whether ACIP should restrict the shingles vaccination 

recommendation to persons <80 years of age. The majority of members supported a recommendation for 

all persons >60 years of age. A minority of members were in favor of restricting the recommendation to 

persons 60-79 years of age only and awaiting additional cost analysis data for this population. 

The workgroup is considering several issues to decide on these two options. Persons >80 years of age 

are included in the package label. No specific safety concerns have been identified in this population. 

Vaccine efficacy against shingles is low in this age group with 0 confidence intervals. The SPS study was 

large, but power to detect effects was lower in persons >80 years of age. Vaccine efficacy would be likely 

in the context of results in younger cohorts. The risk of developing PHN and pain from shingles is 

reduced in vaccinees >80 years of age. Durability of protection from the vaccine out to four years was 

lowest in persons >80 years of age. The incidence of shingles and the risk of pain and PHN were found 

to be highest in the oldest population. However, persons >80 years of age are the most vulnerable and 

least aggressive age group to seek care. This population has the weakest ability to tolerate medications 

for controlling PHN and pain due to co-morbidities and poly-pharmacy. 

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ACIP Meeting Minutes June 29-30, 2006 Page 70 

In addition to the three draft recommendations, the workgroup is also requesting ACIP’s guidance on 

other issues for shingles vaccination. First, should ACIP give consideration to additional groups? These 

populations would include (1) mildly immunosuppressed persons with diabetes or patients on low-dose 

steroids, TNF-blockers and other immunomodulatory drugs; (2) persons with a prior episode of shingles 

because this population has not been formally studied to date; and (3) currently immunocompetent 

persons with an anticipated immunosuppressed status and a high risk of shingles, such as pre-transplant 

patients, early asymptomatic HIV patients, and patients who will undergo chemotherapy or 

immunosuppressive therapy for cancer, rheumatoid arthritis, lupus or other autoimmune diseases in the 

future. 

Second, should ACIP address implementation issues? These recommendations would include (1) 

administration of the vaccine with the next scheduled visit, catch-up vaccination or another approach; (2) 

concomitant administration with pneumococcal, influenza and other adult vaccines; and (3) vaccine 

storage issues. Third, should ACIP provide guidance on post-marketing surveillance? These 

recommendations would include monitoring vaccine safety and duration of protection and identifying the 

need for boosters. 

Dr. Poland expressed concern about ACIP delaying its vote on the shingles vaccine until the next 

meeting. He listed several reasons for ACIP to take action at this time. One of the largest published 

vaccine efficacy studies in history has demonstrated high morbidity rates of shingles among 1 million 

persons in the United States. Solid data have shown that the vaccine is cost-effective, safe and effective. 

HCWs and the public have expressed strong interest in the vaccine. FDA has licensed the vaccine. The 

manufacturer proposes to conduct one of the most extensive sets of post-marketing studies that has ever 

been implemented for a vaccine in history. Financing issues cannot be resolved until ACIP issues formal 

recommendations for use of the vaccine. Dr. Poland raised the possibility of placing a notice in the 

Federal Register of ACIP’s vote on the shingles vaccine at this time and calling the vote by telephone. 

Dr. Anne Schuchat, of CDC, emphasized that ACIP’s vote on the shingles vaccine would be illegal and 

inappropriate from a federal perspective at this time because the public was not given advance notice. 

However, she pointed out that the time leading up to the October 2006 ACIP meeting could be used to 

present additional cost analyses, gather other data, identify outstanding gaps and answer the 

workgroup’s questions. Drs. Abramson and Pickering added that ACIP votes must be published in the 

Federal Register at least 15 days in advance of a meeting. A notice was not published about ACIP’s vote 

on the shingles vaccine. This requirement can be overruled in the event of a disease outbreak or other 

“emergency,” but the shingles vaccine does not meet this criteria. 

Dr. Neuzil made a formal statement for the record in her role as ACIP’s liaison to ACP. ACP is the

nation’s largest medical specialty society with ~120,000 members representing general internists and 

sub-specialty physicians. The Adult Immunization Advisory Committee (AIAC) oversees ACP’s vaccine 

issues and strongly favors a universal recommendation for all immunocompetent adults >60 years of age 

to receive HZ vaccine. AIAC’s position is that this recommendation would be consistent with evidence 

from a high-quality and randomized controlled trial that supports the safety and efficacy of the vaccine. 

The recommendation would also address the substantial burden of illness and suffering associated with 

HZ. AIAC’s overall opinion is that a universal recommendation is the only strategy to ensure optimal 

uptake and access to the vaccine for all eligible patients. 

Dr. Sandra Fryhofer is a member of the ACP AIAC. As a practicing general internist in Atlanta, Georgia, 

she has first-hand knowledge of the pain, suffering and devastating effect on quality of life caused by 

shingles. Of the total population, 2-3 of every 10 persons will suffer from shingles at some point in their 

lives. The complications from shingles can range from an uncomfortable rash to eye and skin problems, 

scarring, nerve paralysis, pneumonia, encephalitis or death. Excruciating pain from PHN can last for 

months or years and may be more severe than chronic cancer pain, post-surgery pain or labor pain 

This document has been archived for historical purposes.
according to pain comparison scores. Data show that the shingles vaccine can reduce the number of 

cases by 50% and decrease overall pain by 40%. Dr. Fryhofer urged ACIP to issue a universal 

recommendation for the shingles vaccine to all eligible persons >60 years of age to ensure no individual 

in need will be denied access to the benefits of the vaccine. 

Childhood/Adolescent Immunization Schedule (CAIS) for 2007 

Dr. Calugar described ongoing efforts by the Childhood/Adolescent Immunization Workgroup to develop 

the 2007 CAIS and refine the existing format. In 1983, the childhood immunization schedule included 

vaccines to protect from diphtheria, tetanus, pertussis, measles, mumps, rubella and polio. At this time, 

children received five shots by 2 years of age and no more than one shot at a single visit due to the 

combination of the DTP and MMR vaccine and oral administration of the polio vaccine. By 1996, the 

childhood immunization schedule included the addition of the varicella and Hib vaccines; the inclusion of 

new recommendations for HepB vaccine, including its use in adolescents; the introduction of colored bars 

for catch-up vaccination and ranges of acceptable ages for vaccines; and other significant modifications. 

Since 1983, the CAIS has been increasingly more complex. The current CAIS covers 14 vaccines and 

ages 0-18 years. Yellow bars represent the range of recommended ages; green bars represent catch-up 

immunization; a purple column emphasizes the importance of the visit at 11-12 years of age; and a red 

box describes special populations. Italics are used to emphasize that the HepB vaccine dose at 4 months 

of age is permissible if combination vaccines were used after the birth dose. Italics are also used to 

underscore that the Hib vaccine at 6 months of age is not required if PedVaxHIB or COMVAX vaccines 

were administered. 

The workgroup updates the CAIS each year with new ACIP recommendations, but the members 

recognized that additional efforts must be made for 2007. Most notably, the rotavirus and quadrivalent 

HPV vaccines were licensed and recommended in 2006. ACIP approved new policies for existing 

vaccines in 2006. Influenza vaccination recommendations were extended to children 24-59 months of 

age and dose 2 of the varicella vaccine was approved. CDC staff, the CDC hotline and workgroup 

members routinely receive feedback on the CAIS from the field. The most common concerns are related 

to the CAIS being overcrowded and overwhelmed with pictures and information; the need for a better 

approach than italics for the HepB vaccine dose at 4 months of age; and the poor appearance of the 

purple bar for the assessment at 11-12 years of age. Some HCWs reported that the footnotes are too 

detailed, while others supported more informative and comprehensive footnotes. 

Concerns from the field and the increasing complexity of the CAIS prompted the workgroup to develop a 

better and more user-friendly format while incorporating ACIP’s new recommendations into the 2007 

CAIS. To undertake this effort, the workgroup partnered with the University of Michigan Child Health 

Evaluation and Research Unit to conduct focus groups with 102 pediatricians, family practitioners, public 

and private-sector immunization providers, and nurses. The focus groups were held in diverse settings, 

including private pediatric and family practice offices, adolescent and school-based clinics, local public 

health departments, federally qualified health centers, and an open session for immunization providers 

during the National Immunization Conference. 

The focus groups were designed to address three major topics: (1) feedback on the current CAIS; (2) 

impressions about several alternative formats the workgroup developed based on previous input; and (3) 

changes to include in future CAISs. Key results of the focus group discussions are summarized as 

follows. The respondents generally agreed on six issues. Separate childhood and adolescent schedules 

would be helpful and easier to read. The color legend should be placed on the side rather than the 

bottom of the CAIS. The purple bar for the assessment at 11-12 years of age should be deleted. The red 

ACIP Meeting Minutes June 29-30, 2006 Page 71 

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ACIP Meeting Minutes June 29-30, 2006 Page 72 

dotted box for special populations is confusing and a colored bar should be used instead. Footnotes in a 

bulleted rather than paragraph format would be easier to read. Placement of the minimum age at 

vaccination in the footnotes was preferred. 

Opinions about the following issues varied among respondents. Some respondents believed the 

italicized text for the HepB vaccine was overwhelmed by other information and could be confused as a 

four-dose series. Other respondents noted that the italicized text clarified the administration of only three 

the HepB vaccine shots. The respondents believed the italicized text for the Hib vaccine at six months 

was useful in reflecting differences in administration of different products, but agreement was not reached 

on a clear approach to distinguish among various brands. 

The respondents did not believe the existing format for meningococcal conjugate vaccine (MCV4) 

reflected usual practice. Several respondents pointed out the need to emphasize MCV4 vaccination of 

adolescents at high school entry. The respondents questioned the order of vaccines in the CAIS. The 

respondents did not reach agreement on the overall format for the adolescent component of the CAIS. 

The respondents noted that catch-up vaccination should be emphasized, but the recommendations 

should not be overwhelmed with colors and other features. Some respondents supported shorter 

footnotes because the Red Book, web sites and other resources could be reviewed for additional 

information. Other respondents were in favor of more detailed and comprehensive footnotes because 

providers do not have sufficient time during routine practice to locate additional references. 

The workgroup is now proposing that the following changes be made to the CAIS based on the focus 

group results. The color legend should be placed on the side. Special populations should be 

represented with purple bars. The red box should be deleted. Vaccines should be placed in 

chronological order of administration. Users of the CAIS should be referred to footnote 1 to obtain more 

information about permissible administration of the HepB dose at four months of age when combination 

vaccines are given after the birth dose. ACIP’s rotavirus vaccine recommendation should be abbreviated 

in the CAIS as “Rota.” 

The italicized font for Hib vaccine at six months of age should be retained because this approach was 

well accepted by most focus group respondents. Influenza immunization should be extended through 59 

months of age for consistency with ACIP’s recommendation. In anticipation of changes to the varicella 

vaccine recommendation, the CAIS should be revised to illustrate the administration of dose 1 at 12-15 

months of age and dose 2 at 4-6 years of age. The footnotes should be reorganized into a bulleted 

format. The minimum age for administration of each vaccine should be highlighted on the first line of 

each footnote. Two special bullets should be incorporated for the HepB dose at 4 months of age and 

brand names of the Hib vaccines. 

Schedules for age groups of children 0-6 years and 7-18 years should separated based on responses by 

immunization providers to several alternative drafts of the CAIS. For the schedule of children 7-18 years 

of age, the color legend should be placed on the side. The purple column for the assessment at 11-12 

years of age should be deleted. This visit should be emphasized with the title and all vaccines in the 

column in bold. Tdap, the HPV series and MCV4 should be placed at the top of the column due to the 

importance of these vaccines during the young adolescent visit. The footnotes should be reorganized 

into a bulleted format. Based on the focus group results, the workgroup developed two drafts of the new 

immunization schedule for children 7-18 years of age with the same content and different formats. 

“Alternative B” was designed with dashed colored lines rather than bars. 

The workgroup will take several actions in preparation of the October 2006 ACIP meeting. The focus 

group research will continue. Collaborative efforts will be undertaken with subject matter experts on the 

content of the footnotes and catch-up schedule. Field tests will continue to be conducted to obtain input 

on the schedule for children 0-6 years of age; the preferred format for the schedule for adolescents 7-18 

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years of age; updates to catch-up schedules; and black-and-white formats. A decision will be made on 

the best approach to convey information about MCV4 immunization because the focus group 

respondents pointed out that MCV4 catch-up vaccination during the high school entry visit might create 

confusion among providers. The workgroup intends to present and solicit ACIP’s approval on the final 

schedule during the October 2006 meeting and publish the approved schedule in the MMWR in January 

2007. 

Dr. Middleman strongly recommended developing a separate adolescent immunization schedule due to 

the dramatic shift in the care of children at 11-12 years of age. Most notably, morbidity and mortality from 

risky behaviors serve as the primary risk to this age group rather than vaccine-preventable diseases. She 

pointed out that a separate adolescent immunization schedule and a solid statement about the 

importance of adolescent immunization as a component of broader care would emphasize the shift in 

care and strengthen general preventive care and healthcare visits in this population. 

Dr. Middleman noted that a separate adolescent schedule would also underscore the importance of 

immunization, highlight the critical need for preventive care across the life span, and provide a strong link 

between adolescent and adult immunizations. This change could play a significant role in advancing the 

adolescent preventive care field and enhancing other types of care in this traditionally underserved 

population. 

On the one hand, Dr. Poland and Ms. Stinchfield were in favor of Dr. Middleman’s suggestion for a 

separate immunization schedule for adolescents beginning at 11 years of age. If ACIP approves the 

recommendation, Dr. Poland urged CDC to develop the childhood and adolescent immunization 

schedules with similar formats to the adult immunization schedule. Dr. Georges Peter, of Brown Medical 

School, served on NVAC when the recommendation was adopted to change the “pediatric immunization 

standards” to “childhood and adolescent immunization standards.” He pointed out that Dr. Middleman’s 

suggestion for separate immunization schedules for pre-adolescent and adolescent age groups would be 

consistent with the terminology NVAC previously approved. 

On the other hand, Dr. Calugar noted that the focus group results differed from Dr. Middleman’s 

suggestion. Although most respondents also supported separate childhood and adolescent immunization 

schedules due to programmatic issues, children 0-6 years and adolescents 7-18 years were the preferred 

age cutoffs between the two groups. Dr. Gary Freed, the NVAC liaison, emphasized the critical need to 

apply feedback from practitioners in the field who actually use the CAIS. 

Dr. Wallace confirmed that CDC and the Childhood Adolescent Immunization Workgroup would use the 

focus groups to more vigorously test the adolescent schedule. Collaborative efforts would also be 

undertaken with AAP, SAM and other relevant groups to develop and pilot alternative immunization 

schedule formats prior to the October 2006 ACIP meeting. Dr. Wallace mentioned that CDC and the 

workgroup would also need to address requests from the field to issue immunization schedules for all age 

groups at the same time. Dr. Abramson asked the workgroup to report on the field test results of the 

alternative immunization schedule formats during its presentation to ACIP in October 2006. 

Update on the Multi-State Mumps Outbreak in the United States 

Dr. Jane Seward, of CDC, reported on the U.S. mumps outbreak that occurred in 2006 with a comparison 

to the U.K. mumps outbreak of 2004-2005. The mumps vaccine was licensed in the United States in 

1967 and a routine childhood recommendation was made in 1977. Mumps cases substantially declined, 

however, a resurgence in mumps cases occurred in the late 1980s. A two-dose measles, mumps and 

rubella (MMR) schedule was implemented in 1989 that contributed to a dramatic decline in mumps cases 

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ACIP Meeting Minutes June 29-30, 2006 Page 74 

with <300 cases reported each year since 2001. In 1998, the Healthy People 2010 goal was established 

to eliminate indigenous mumps transmission in the United States. Despite the small number of cases 

reported each year, some small, isolated outbreaks have occurred. 

For example, in February 2006, CDC published a report in the MMWR of a mumps outbreak that occurred 

at a New York State summer camp in 2005 with 31 cases of unvaccinated counselors and two-dose 

vaccinated campers. The index case was identified as an unvaccinated camp counselor from the United 

Kingdom. In March 2006, CDC published a dispatch in the MMWR of a mumps epidemic of ~600 cases 

that occurred in Iowa in 2006. 

CDC took several actions in response to the outbreaks. Activities were coordinated at the national level 

with ACHA, CTSE and the Association of Immunization Managers. Information was shared with public 

agencies and private organizations. Guidance documents were distributed to summer camp associations 

and healthcare settings. The media were alerted and documents were placed on the CDC web site. A 

national health advisory was issued. Several CDC divisions provided technical support and expertise to 

support mumps surveillance and clinical activities, epidemiological investigations and laboratory 

diagnostics. 

CDC used its National Notifiable Disease Surveillance System (NNDSS) as a key data source during the 

mumps outbreaks. CDC also received biweekly reports of mumps cases from states with case 

classifications, hospitalizations and deaths to ensure that data would be timely and consistent with 

information posted on state web sites. CDC collaborated with affected states and published an updated 

dispatch on the multi-state mumps outbreak in the MMWR in May 2006. Of 4,602 cases reported as of 

June 20, 2006, 1,940 were from Iowa and 1,920 were from seven other outbreak-related states (OB-7): 

Illinois, Kansas, Missouri, Nebraska, Pennsylvania, South Dakota and Wisconsin. Five states had travelrelated cases or cases related to temporary residence in one of the mumps outbreaks. The outbreaks in 

Iowa and the OB-7 states peaked between the weeks of April 8-May 6, 2006 and then declined. 

Of 3,680 cases reported from Iowa and the OB-7 states, 65% were among females. The median age of 

cases was 22 years with a range from <1-96 years. NNDSS provisional data showed that the incidence 

of mumps per 100,000 persons in all eight outbreak-related states ranged from 65.3-0.7 with the highest 

rates in Iowa, Kansas, South Dakota and Nebraska. However, incidence rates are expected to increase 

in Wisconsin and Illinois because NNDSS reports from these states are not up-to-date at this time. By 

age group, the incidence of mumps cases was highest in persons 18-24 years in all eight outbreakrelated states. 

Mumps cases primarily occurred among college students and HCWs, but a few outbreaks were reported 

in schools and child care centers as well. Transmission remained fairly focused with little or no spread to 

infants or populations that refused vaccine. As of June 17, 2006, Iowa reported that 7% of its cases were 

unvaccinated, 14% had received one MMR dose, 50% had received two MMR doses, and 30% had an 

unknown vaccination status. However, CDC acknowledges that reporting information on vaccination 

status of cases through NNDSS is incomplete and is now encouraging states to submit up-to-date 

information. 

Laboratory data of the 2006 mumps outbreaks showed isolation of the G genotype from 21 specimens 

submitted by nine states. Clinical data reported through NNDSS showed that 81% of 3,860 mumps 

cases had a history of parotitis and some cases reported serious complications, including meningitis, 

encephalitis, orchitis, deafness or hospitalization. However, 11 of 66 hospitalizations reported by the 

state biweekly reports were not related to mumps. No deaths were reported among any of the mumps 

cases. Preliminary data from CDC’s epidemiological and laboratory investigations showed attack rates of 

2% and 3.8%, respectively, in two highly affected college campuses in Iowa. Coverage rates of two MMR 

doses were found to be 97% and 77%, respectively, among college students at these two campuses. 

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CDC’s college roommate contact study in Iowa showed a vaccine failure rate of ~8% among two-dose 

recipients. 

CDC is partnering with several groups in other epidemiological and laboratory investigations. The 

sensitivity and specificity of immunoglobulin M (IgM) test kits that are not FDA-approved are being 

compared to the CDC capture assay in collaboration with Iowa and Wisconsin state health laboratories. 

A waning immunity study was completed at an unaffected college campus in Nebraska with 450 MMR 

two-dose students in collaboration with FDA and Merck. Cross-neutralization studies are underway in 

collaboration with FDA, Merck and Japanese agencies. CDC will continue to partner with the Kansas and 

Iowa public health departments to conduct additional studies on vaccine coverage, efficacy and failure; 

viral shedding; mumps risk factors in college settings; attitudes and adherence to isolation; costs of the 

mumps public health response; and infection control and nosocomial transmission among HCWs. 

The large U.K. mumps outbreak occurred in 2004-2005 with 72,000 reported cases and the highest 

incidence among persons 15-24 years of age. The U.K. and U.S. epidemiology differed because 67% of 

cases were unvaccinated in the United Kingdom, 30% had received one MMR dose, and 3% had 

received two MMR doses. The U.K. mumps incidence was 20-50 times higher than in the United States 

prior to the outbreak and 70 times higher during the outbreak based on an assumption of 5,000 cases in 

the U.S. outbreak. 

Differences in the U.S. and U.K. mumps vaccination programs played a key role in the higher incidence in 

the United Kingdom. For example, the U.S. mumps vaccination program was established 21 years 

before the U.K. program. The United States implemented a two-dose MMR schedule seven years before 

the United Kingdom. Coverage of one MMR dose in the United States is 11% higher than the United 

Kingdom. Coverage of two MMR doses in the United States is >20% higher than the United Kingdom due 

to U.S. school entry requirements. 

CDC used ACIP’s 1998 MMR statement and the joint 1997 ACIP/Healthcare Infection Control Practices 

Advisory Committee (HICPAC) recommendations as policy to guide outbreak response to the mumps 

outbreak. However, discrepancies were identified between policy and evidence of immunity. On the one 

hand, ACIP’s MMR statement recommended two doses for school-age and college-age students for 

measles control and elimination. The ACIP/HICPAC guidance for HCWs recommended a one-dose 

mumps policy, placed minimal emphasis on the importance of mumps immunity, and merely stated that 

immunity to mumps would be “highly desirable.” On the other hand, the evidence of immunity for mumps 

through vaccination supported one dose for all age groups. 

ACIP convened a conference call on May 17, 2006 to address these discrepancies. CDC and the Iowa 

Department of Public Health presented scientific evidence to demonstrate that a second MMR dose 

would provide additional protection and effectiveness of >10%. Key points from ACIP’s updated 

recommendations on the control and elimination of mumps are highlighted as follows. Based on changes 

in evidence of immunity through vaccination, children 1-4 years of age and low-risk adults should receive 

one MMR dose. School-age children, students in post-high school educational facilities, international 

travelers and HCWs should receive two MMR doses. HCWs without other evidence of immunity should 

routinely receive two MMR doses. HCWs born before 1957 should consider one MMR dose in a nonoutbreak setting and should strongly consider two MMR doses during an outbreak. Children 1-4 years of 

age and low-risk adults affected by an outbreak should be given a second MMR dose. ACIP’s updated 

mumps recommendations were published in the MMWR on June 1, 2006. 

CDC has identified several potential reasons for the mumps outbreaks. Importation or the index case 

was not detected. Recognition of the outbreak was delayed because physicians are no longer familiar 

with mumps, the disease has been modified by vaccine, and some early cases were ruled out due to 

negative IgM. Colleges have the potential for high transmission and lower two-dose vaccine coverage 

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than other school settings. Adherence to isolation guidelines may be poor in college settings. Vaccine 

effectiveness of 90% and two MMR doses may result in the accumulation of susceptible persons with 

sufficient capacity to periodically sustain transmission and sizeable outbreaks. Waning immunity could 

contribute to mumps outbreaks. However, CDC acknowledges that high vaccine coverage at the 

community level, vaccine effectiveness and a relatively low incidence rate most likely prevented 30,000-

40,000 mumps cases. 

Dr. Seward and other CDC staff provided additional details on the mumps outbreaks in response to 

ACIP’s questions. 

• The position of several state epidemiologists is that differences in college immunization 

rates most likely played a stronger role than other variables in the mumps outbreaks. 

• CDC is continuing its collaborations with FDA and Merck on neutralizing antibody testing 

to determine susceptibility, seronegativity and a decline in neutralizing antibody levels 

among persons who were vaccinated >15 years previously. 

• The index case in the Boston measles outbreak was identified as a male from India ~35 

years of age with the D8 genotype. Aggressive actions were take to administer >10,000 

MMR doses to persons 25-40 years of age because NHANES data show that this 

population has the highest susceptibility of measles of 20%. The vaccination status was 

unknown in many of the measles cases. 

Dr. Martin Myers, of the National Network for Immunization Information, pointed out that the dissemination 

of inaccurate information on the MMR vaccine in the United Kingdom contributed to the U.K. outbreak in 

addition to differences between the U.S. mumps vaccination program. The distribution of inaccurate 

information in the United Kingdom may have played a role in the U.S. mumps outbreaks as well. 

Update on the Rotavirus Vaccine 

Dr. Umesh Parashar, of CDC, described activities that have occurred since ACIP adopted 

recommendations and passed the VFC resolution for the rotavirus vaccine in February 2006. ACIP’s 

recommendations were submitted to the MMWR on April 5, 2006 and are expected to be published on 

August 11, 2006. Merck data show that from February 6-June 28, 2006, 670,000 doses were distributed 

in both private and public sectors throughout the country. The commercial and VFC prices for the 

rotavirus vaccine were established at $63.25 and $52 per dose, respectively. ACIP’s provisional 

recommendations can now be accessed on the NIP web site. 

Of 22 rotavirus vaccine-related reports submitted to VAERS as of June 23, 2006, two were 

intussusception cases. Case 1 was reported from a study in Mexico of a male child 6 months of age with 

onset of symptoms two days after dose 3. The child had a concomitant common cold and 

intussusception resolved after a second attempt at air enema. Case 2 was a female child 2.5 months of 

age with onset of symptoms six days after dose 1. The child required surgery and resection of necrotic 

bowel. The child’s older sibling had diarrhea 1-2 days prior to the onset of symptoms in the case. CDC is 

now analyzing clinical specimens and tissues from the surgical resection to detect rotavirus, the specific 

vaccine strain, adenovirus or other agents. 

In addition to daily monitoring of VAERS reports by CDC and FDA, other safety monitoring activities of the 

rotavirus vaccine will be conducted as well. CDC will use its VSD birth cohort of ~80,000 infants to detect 

and formally evaluate risk signals that are identified through passive reporting or other mechanisms. 

Merck will conduct active surveillance of a different managed care birth cohort of ~44,000 infants. CDC, 

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FDA and Merck will continue to convene biweekly conference calls to discuss updated data from various 

systems, share information and develop plans for future studies. 

A study that is in press and will be published in Pediatrics in August 2006 provides estimates of the 

number of naturally occurring intussusception cases that would be temporally associated with rotavirus 

vaccination by chance alone (Tai, et al.) In anticipation of concerns raised by such reported cases, CDC 

calculated the number of natural intussusception cases that would occur within two weeks after rotavirus 

vaccination. Vaccine coverage rates for DTaP and the age-specific incidence of intussusception were 

incorporated into the model. The model was designed with a “strict” schedule of vaccine administration at 

2, 4 and 6 months of age and a “free” schedule of vaccine administration any time in the first year of life. 

The results of CDC’s analysis are summarized as follows. After doses 1-3 of the rotavirus vaccine, a total 

of 138 intussusception cases would occur within two weeks with the strict schedule and a total of 182 

cases would occur within two weeks with the free schedule. Thus, within two weeks of administration of a 

rotavirus vaccine dose by chance alone, ~130-180 natural intussusception cases would occur. Most 

cases would occur after doses 2 and 3. Fewer temporally-associated intussusception cases would occur 

with the strict schedule compared to the free schedule. The overall incidence of intussusception per 

100,000 doses would be 4.59 cases with the strict schedule and 4.76 cases with the free schedule. 

In addition to monitoring the safety of the rotavirus vaccine, CDC will also monitor its effectiveness. The 

existing New Vaccine Surveillance Network with sentinel sites at Cincinnati, Rochester and Vanderbilt will 

be used to monitor and evaluate post-licensure vaccine effectiveness against laboratory-confirmed 

hospitalizations and emergency department visits for rotavirus diarrhea. Active and population-based 

surveillance will be performed in three U.S. counties. Specimens will be collected and tested for rotavirus 

from children <3 years of age who are hospitalized or who visit emergency rooms or outpatient clinics for 

diarrhea. Vaccine effectiveness will be evaluated by monitoring disease trends over time and conducting 

a case-control study in the field. 

CDC will use its existing laboratory network of 12 laboratories throughout the country to monitor the 

impact of the rotavirus vaccine against virus strains. To date, the laboratory network has characterized 

~3,000 strains. CDC will apply the surveillance system prospectively to identify unusual strain patterns 

that emerge in the future. 

Ex Officio Reports

NVAC. Dr. Gary Freed covered the following areas in his first ex officio report to ACIP as the new NVAC 

Chair. NVAC was recently charged with addressing vaccine financing. The IOM’s two previous studies 

on this issue did not lead to conclusions that were universally accepted or adopted. The inability to reach 

agreement on this topic to date is based on two different perspectives in the vaccine financing 

community. On the one hand, some persons believe the entire system is damaged and a completely new 

process should be developed. On the other hand, some persons believe specific components of the 

current vaccine financing system are sub-optimal and contain significant gaps. Moreover, new 

recommendations and government programs create problems or emphasize particular elements in the 

current system that should be changed. 

Dr. Freed announced that NVAC will most likely address specific components of vaccine financing 

associated with the most significant problems at this time. NVAC will achieve this goal by convening a 

new Vaccine Financing Workgroup over the next three months with representation by NVAC, ACIP and 

selected professional organizations, and governmental agencies. Other interested groups will be 

provided opportunities to give testimony or make presentations to the workgroup. NVAC’s preliminary 

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discussions to date have resulted in general agreement to charge the workgroup with identifying optimum 

solutions to improve the financing of vaccines for children, adolescents and adults throughout the nation. 

Health Resources and Services Administration (HRSA). Dr. Geoffrey Evans covered the following 

areas in his report for HRSA. As of April 2006, >5,000 claims were submitted in response to the Omnibus 

Autism Proceeding. The hearing on the autism and autism spectrum disorder litigation is expected to be 

held in late 2007 or early 2008. The first phase of discovery and data collection is nearly complete. The 

court has given petitioners a deadline of 2006 to early 2007 to submit expert witness reports for the next 

phase of the litigation. Based on results of a recent industry survey to manufacturers of all vaccines 

covered under the National Vaccine Injury Compensation Program, the number of vaccine lawsuits is 

extremely low with the exception of the ongoing autism litigation. 

Dr. Evans announced that legislation is pending in both the House and Senate to add an excise tax for 

the conjugate and polysaccharide meningococcal vaccines. A bill was also recently introduced in the 

House to add an excise tax for the HPV vaccine. The U.S. Court of Appeals for the Federal Circuit made 

three decisions in 2005 and 2006 that would relax the standard for the claims court to make a ruling on 

off-table vaccine claims. Based on two decisions, the Special Master could rely on medical records and 

medical opinion, but would not be required to use scientific literature. Several claims court judges have 

reversed vaccine claims based on these two decisions. Dr. Evans committed to providing ACIP with 

regular updates on all three decisions as new developments occur. 

NIH. Dr. George Curlin covered the following areas in his report for NIH. HHS and NIH are supporting 

several manufacturers to produce H5N1 influenza vaccines for clinical testing at NIH. The clinical trials 

are designed to assess vaccine safety and determine whether certain adjuvants or routes of 

administration can improve immunogenicity of influenza vaccines. NIH’s vaccine studies for influenza 

viruses with pandemic potential are being conducted by various manufacturers and cover multiple 

viruses, age groups and vaccine types. Research is also being planned to analyze strategies to optimize 

the dose required to protect persons against pandemic influenza. 

Novartis, sanofi pasteur and Baxter are now conducting studies of inactivated H5N1 influenza vaccines, 

while MedImmune will conduct a study of the H5N1 LAIV in the future. Novartis and sanofi pasteur are 

currently analyzing and verifying safety and immunogenicity data on use of inactivated vaccines in adults, 

children and elderly persons. The studies are also analyzing inactivated vaccines on the basis of an 

adjuvant and an intradermal versus intramuscular route of administration. The manufacturers expect to 

produce reports from these studies later in 2006. In January 2006, sanofi pasteur published a report in 

the New England Journal of Medicine on prime and booster doses of a two-dose inactivated vaccine 

schedule for adults. Dr. Curlin encouraged ACIP and members of the public to access 

www.clinicaltrials.gov to obtain additional information on all of NIH’s clinical trials. 

Public Comment Period 

Ms. Laura Bono, of the National Autism Association, made the following comments for ACIP’s 

consideration. Her son was developing normally at 16.5 months of age, but his speech and social skills 

discontinued soon after receiving four different vaccines on the same day. The 50 μg of thimerosal he 

received from the four shots were 45 times the EPA limit for mercury for an infant of his weight. Her son 

is now 17 years of age and has been diagnosed with ~20 different conditions caused by mercury toxicity 

since receiving the four shots at 16.5 months of age. 

Ms. Bono pointed out that experts from CDC and other groups have made public statements about the 

risks of thimerosal-containing vaccines. However, data on the subset of children who develop autism 

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from thimerosal-containing vaccines have been deleted from research to avoid embarrassing NIP. A 

study that showed no association between thimerosal and autism was published in Pediatrics in 

November 2000. 

Ms. Bono further noted that misguided and uninformed policymakers are approving heavy metalcontaining vaccines without knowledge of the most recent research on heavy metal toxicity. She 

emphasized the critical need for ACIP and other vaccine policymakers to take four important actions. 

One, appropriate heavy metal toxicity tests should be conducted before vaccines are approved. Two, 

research should be performed on the relationship between thimerosal and autism. Three, the issue of 

“safe” vaccines should always be paramount during the decision-making and approval process. Four, 

ACIP should state a preference for thimerosal-free and aluminum-free vaccines for pregnant women and 

children. 

Cmdr. Stephen Kay, of the U.S. Navy, made the following comments for ACIP’s consideration. His son 

was developing normally after his birth in April 1999, but he began displaying traditional autistic 

characteristics soon after receiving 281.37 μg of mercury from routine immunizations during his first year 

of life. His son is now 7 years of age and was diagnosed with mercury poisoning in 2003. The 

developmental pediatrician who made the diagnosis gave his son no longer than three months to live if 

the mercury poisoning had not been detected at that time. His son’s speech, social skills and other 

developmental milestones are no longer comparable to other children his age. The financial responsibility 

in providing medical care for his son continues to place an enormous burden on the entire family. On 

behalf of his son and other similarly affected children, Cmdr. Kay urged ACIP to recommend thimerosalfree and aluminum-free vaccines. 

Mr. Scott Bales is the Vice President of the Autism Society of America-Georgia Chapter. He made the 

following comments for ACIP’s consideration. Mr. Bales is 48 years of age and attributes his autism to 

vaccines that were administered to him as an infant, but are now banned. He described several 

challenges encountered by the vast majority of the adult autism population, such as chronic sensory 

problems, allergies and other health issues; frequent emergency department visits; sexual exploitation; 

dependence on others for care; reliance on public financial assistance programs; and an inability to obtain 

and retain employment. He conveyed that adults with autism are unique compared to adults with other 

conditions. Most notably, organizations for cerebral palsy, muscular dystrophy and other “physical” 

disabilities have no interest in including or assisting autistic adults due to the complexity of this disease. 

Mr. Bales urged ACIP to recommend the removal of heavy metals from vaccines. 

Closing Session 

Dr. Abramson thanked the ACIP members, liaison and ex officio representatives, and members of the 

public for attending and participating in the meeting. 

With no further discussion or business brought before ACIP, Dr. Pickering adjourned the meeting at 3:31 

p.m. on June 30, 2006. 

 I hereby certify that to the best of my knowledge, 

the foregoing Minutes of the June 29-30, 2006 

ACIP Meeting are accurate and complete. 

ACIP Meeting Minutes June 29-30, 2006 Page 79 

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ACIP Meeting Minutes June 29-30, 2006 Page 80 

___________________ ______________________________________ 

Date Jon S. Abramson, M.D., Chair, 

Advisory Committee on Immunization Practices 

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