Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

Agenda – Final 3/21/08 

Interagency Vaccine Group (IAVG) 

Meeting on the Development of CDC’s 

Immunization Safety Office (ISO) 

Research Agenda 

August 3, 2007, Washington D.C. 

Meeting Summary 

Disclaimer: The ideas and recommendations of this report reflect those of federal 

scientists. This report does not represent Centers for Disease Control and Prevention 

(CDC) or Department of Health and Human Services policy, nor does it necessarily 

reflect which ideas will be incorporated into CDC’s final Immunization Safety Office 

Research Agenda. 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Background 

The Centers for Disease Control and Prevention’s (CDC) Immunization Safety Office 

(ISO) is developing a comprehensive, scientifically robust research agenda with 

extensive input in a transparent manner. ISO is working with the National Vaccine 

Program Office (NVPO) and National Vaccine Advisory Committee (NVAC) to respond 

to a recommendation from the 2005 Institute of Medicine (IOM) report: “Vaccine Safety 

Research, Data Access, and Public Trust.” IOM recommended that a subcommittee of 

NVAC advise CDC on the Vaccine Safety Datalink (VSD) Project research agenda. 

Because carrying out high-quality research requires integration across the ISO research 

and surveillance components, the scope will include the full ISO research agenda, 

including the VSD Project. 

In this context, ISO collaborated with NVPO to obtain input from Federal scientists to 

inform development of the ISO draft research agenda before the NVAC scientific review. 

ISO solicited input from Federal scientists representing relevant Department of Health 

and Human Services (HHS) and Department of Defense (DoD) agencies and programs 

during an Interagency Vaccine Group (IAVG) meeting, convened by NPVO in 

Washington, D.C. on August 3, 2007. HHS meeting participants included representatives 

from the NVPO, FDA, NIH, HRSA, and CDC. All participants received briefing 

materials, including the charge, before the meeting. A summary of the meeting is 

provided below. Additional information from the meeting’s brainstorming sessions is 

available in Appendix A. 

In Attendance: 

COL Randall G. Anderson 

Robert Ball, M.D., M.P.H. 

Kenneth Bart, M.D., M.P.H. 

Brigid Batten, M.P.H. 

CDR Karen R. Broder 

Carmen M. Collazo, Ph.D. 

George Curlin, M.D. 

COL Renata J.M. Engler 

Geoffrey Evans, M.D. 

LT Kent Forde 

Paul M. Gargiullo, Ph.D. 

Bruce Gellin, M.D., M.P.H. 

Marion Gruber, Ph.D. 

LTC Wayne Hachey 

 Florence Houn, M.D. 

CDR John Iskander 

Rosemary Johann-Liang, M.D. 

Laura Leidel, M.S.N., M.P.H. 

Bill G. Kapogiannis, M.D. 

Feng-Ying (Kimi) C. Lin, M.D. 

Alison Mawle, Ph.D. 

Karen Midthun, M.D. 

Jennifer Reid, M.D. 

Dan Salmon, Ph.D. 

CAPT Ben Schwartz 

LCDR Angela Shen (by phone) 

Barbara Slade, M.D., M.S. (by phone) 

Dixie Snider, M.D., M.P.H. 

 (Rear Admiral, retired) (Chair)

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Welcome—John Iskander 

CDR John Iskander welcomed the participants and thanked them for their attendance. He 

spoke briefly of the events leading to the present meeting. 

In 1986, Congress asked the Institute of Medicine (IOM) to assess the causal relationship 

between vaccines and purported adverse events. The IOM found that, in two-thirds of the 

cases investigated, there was inadequate scientific evidence to determine that 

relationship. The IOM gave the following reasons for the limitations in knowledge at that 

time: 

• An inadequate understanding of the biologic mechanisms underlying adverse 

events; 

• Inconsistent information from case reports and case series; 

• Inadequate size and followup of many population-based epidemiologic studies; 

and 

• Limitations of existing surveillance systems. 

To address these problems, the CDC created the the Vaccine Adverse Event Reporting 

System (VAERS), in collaboration with the Food and Drug Administration (FDA), the 

Vaccine Safety Datalink (VSD) Project, and the Clinical Immunization Safety 

Assessment (CISA) Network. 

CDR Iskander addressed the reasons for the remaining gaps in our knowledge of vaccine 

safety. These include the rarity of serious adverse events, the difficulty of conducting 

high-quality scientific studies, the relative infancy of vaccine safety as a science, and the 

large number of licensed vaccines and of alleged vaccine-related adverse events. 

Though, in 2005, ISO’s mission refocused on vaccine risk assessment, CDR Iskander 

noted that the ISO remains in engagement with broader science and policy initiatives 

concerned with vaccine safety. 

ISO Program Overview, Research Agenda Development Process, and Meeting 

Organization—Karen Broder 

CDR Karen Broder said that the ISO works with US and international partners to develop 

and support research to identify adverse events after vaccination and to assess their 

causality and risk factors, to communicate the results of research, and to establish 

scientific methodology and standardize case definitions for vaccine adverse events. 

Key ISO research and surveillance components include 

• VAERS, a passive surveillance system that identifies vaccine safety signals of 

possible concern and allows the formation of hypotheses; 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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• The Brighton Collaboration, offering standardized case definitions to provide a 

common vocabulary for vaccine research and surveillance; 

• The VSD, a collaboration between the Centers for Disease Control and Prevention 

(CDC) and eight managed care organizations (MCOs) with comprehensive 

medical and immunization histories of 5.5 million people per year; VSD is a 

resource for testing hypotheses and conducting surveillance; and 

• CISA, a collaboration of the CDC with six academic centers to study the 

pathophysiology of adverse events, identify risk factors, and offer evidence-based 

guidance for clinicians. 

In 2005, the IOM recommended that a subcommittee of NVAC advise CDC on the 

Vaccine Safety Datalink (VSD) Project research agenda. In response, ISO is 

developing a comprehensive research agenda with extensive internal and external 

input. The research agenda development is currently structured as a three-phase 

process: CDC develops a draft agenda; the National Vaccine Advisory Committee 

(NVAC) facilitates a scientific review of the draft; and CDC finalizes the agenda, 

taking the NVAC feedback into account. 

A meeting of external scientific consultants was held in May of 2007. CDR Broder 

discussed the composition of the body of consultants, the charge to the group, the 

framework of that meeting, and the areas of research they suggested. 

CDR Broder then described the charge to the participants of the present meeting. 

Participants were asked to identify: 

• Vaccine safety topics that are, or will be, important for public health and could be 

studied by the ISO; 

• Vaccine safety research priorities; and 

• Areas for research collaboration between the ISO and other Federal programs. 

The VSD Project—Paul Gargiullo 

Dr. Gargiullo began by outlining the historical background of the project, noting that the 

VSD was established in 1990 to monitor immunization safety and address the gaps in 

scientific knowledge about rare and serious events following immunization. The VSD 

incorporates demographic data such as age and gender, vaccination records, and 

diagnoses in the form of ICD9 codes and offers the ability to review medical charts. Dr. 

Gargiullo said that, in practice, the codes are used to cast a wide net, while the charts 

furnish specificity. VSD data support cohort, case control, case series, and sequential 

monitoring studies. Limited access minimizes the risk of loss of confidentiality. 

The VSD Project MCO sites are: 

• Group Health Cooperative of Puget Sound, Seattle, WA, US 

• Kaiser Permanente Northwest, Portland, OR, US 

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• Kaiser Permanente Medical Care Program of Northern California, Oakland, CA 

• Southern California Kaiser Permanente Health Care Program, Los Angeles, CA 

• HealthPartners Research Foundation, Minneapolis, MN 

• Marshfield Clinic Research Foundation, Marshfield, WI 

• Kaiser Permanente Colorado, Denver, CO 

• Harvard Pilgrim Health Care, Boston, MA 

More than 85 articles using VSD data have been published in peer-reviewed journals; 

more than 75 studies are now in progress. Current studies are looking at the safety of 

newly licensed vaccines, evaluating the safety implications of new recommendations for 

existing vaccines, examining clinical disorders following immunization, and assessing 

vaccine safety in special populations. 

Dr. Gargiullo noted that the possibility of continuous monitoring of newly licensed 

vaccines has stimulated the development of new statistical methods. He discussed selfcontrol case series methodology in which the probability of an adverse event during a 

defined risk period (following vaccination) is compared with the probability during 

control periods for the same person. He also noted that different statistical methods may 

be combined to fit epidemiological needs. 

Dr. Gargiullo discussed the origin of VSD research ideas and the process of initiating and 

performing VSD studies. He noted that the number of researchers wanting access to VSD 

data make prioritization a critical issue. 

Dr. Gargiullo also addressed current challenges facing the project. These include the need 

to expand the number of MCOs providing adult data, the trade-off between timeliness 

and quality of vaccine safety studies, public perception of data-sharing issues, and a need 

to be open to the possibility of adverse events that have yet to be considered. 

CISA Network—John Iskander 

The CISA Network has been in existence for approximately 5 years. Its goals are 

• To study the pathophysiology of adverse events following immunization; 

• To identify risk factors associated with the development of adverse events 

following immunization; and 

• To develop evidence-based guidance for use by clinicians. 

The CISA Network sites are 

• Boston Medical Center; 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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• Columbia University Medical Center; 

• Johns Hopkins University; 

• Northern California Kaiser Permanente; 

• Stanford University Medical Center; and 

• Vanderbilt University Medical Center. 

Accomplishments of the CISA Network include 

• The establishment of a registry and repository for the enrollment of persons 

experiencing an adverse event following immunization and for the collection and 

storage of specimens; 

• The development of an algorithm for the management of hypersensitivity 

reactions immediately following vaccination; and 

• Contribution to the characterization and monitoring of adverse events following 

smallpox vaccination of civilian healthcare workers. 

Priorities of research studies are determined by the CISA team leader and ISO director 

after input from CISA team members and principal investigators at the network sites and 

are based not only on CISA’s own goals, outlined above, but on VAERS and VSD 

signals and on the severity or high incidence of particular adverse events. Research 

proposals must be scientifically sound and logistically and financially feasible. 

CDR Iskander outlined the process for initiating a CISA research project, from initial 

discussion of the concept, through presentation to CISA investigators and the 

establishment of working groups, to institutional review board approvals and Health 

Insurance Portability and Accountability Act (HIPAA) data use agreements. He spoke, 

also, of the challenges facing CISA, which include the rarity and geographic dispersion 

of cases, the costliness of clinical and DNA studies, and the maintenance of HIPAA 

requirements for data privacy. 

CDR Iskander closed his remarks with examples of CISA projects. 

Discussion 

CDR Iskander opened the floor to questions on the presentations on the VSD and CISA. 

In response to a question about how CISA interfaces with other agencies in research, 

CDR Iskander said that the focus is on the feasibility of the proposed study, including the 

feasibility of enrollment, the availability of the required expertise, and an appropriateness 

of fit between the research needs and the agency resources. 

Dr. Gargiullo was asked how many of the 85 papers published using VSD data required 

chart review. He replied that most do and added, because the question implied a concern 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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regarding the time a study could take, that it is rare that a VSD study is complete within a 

few years. 

This led to a discussion of research priorities. A participant voiced the concern that 

suggestions from the present meeting would not be in the research queue for years and 

asked for a commitment to shift priorities if the discussion raises issues of immediate 

concern. CDR Iskander replied that that was the intent of the meeting. 

A participant expressed admiration of the case series method that Dr. Gargiullo had 

discussed and asked whether there was ever the temptation to redo earlier studies with 

more recently developed statistical tools. CDR Broder acknowledged that there could be 

such a desire, for several reasons, although for any previous study to be revived, it would 

need to be viable in terms of current research needs. 

Dr. Gargiullo was asked whether the backlog of VSD research projects was due to 

limited resources. He responded that the major difficulty was that there were not enough 

researchers at the MCOs. 

Brainstorming Session 1: Infant and Child 

For each of the brainstorming sessions, CDR Broder provided background information in 

the form of the concerns raised, and suggestions made, at a previous meeting of ISO 

external consultants. She also reviewed US immunization recommendations for civilians 

for each life stage. She reminded the participants that they should 

• Identify the important gaps in our current knowledge; 

• Indicate why these areas were important; and 

• Suggest possible approaches to address the areas identified. 

She noted that the focus would be on the first two of the three tasks but that insights as 

to possible approaches would be welcome. The ideas, she said, could be either thematic 

or specific. 

Following each brainstorming session, participants were asked to fill in a form asking 

for the five most important research topics; this information is summarized in Appendix 

A. 

Dr. Dixie Snider served as moderator for the brainstorming sessions. 

The following were suggested as areas for research or issues of concern. Responses are 

listed in the order in which the suggestions were made. 

• Mumps/measles/rubella vaccine (MMR) and thrombocytopenia—mechanisms 

• Mumps/measles/rubella/varicella vaccine (MMRV) versus MMR and Varivax 

given separately 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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• Reimmunization protocols (challenge/rechallenge) 

– Systematic guidelines for medical exemption following an adverse event, 

including identifying false contraindications 

• Causality assessment, particularly in complex clinical cases 

– Improved data in VAERS to support this 

– Rechallenge reproducibility (worsening of AE) 

• Sudden unexpected death following infant vaccination (up to 18 mo.) 

– Record individual level, birth dose 

– Epidemiological studies, mortality rates 

• How high a priority should thimerosal/autism studies be? 

– Raises questions of communication among physicians, patients, and 

researchers 

– Focus on other neurological conditions than autism 

 – Use the self-control case series statistical method to screen for 

 neurological visits/neurodevelopmental disabilities within specified time 

 periods after vaccination 

– Focus on special populations (e.g., low birth weight) 

– Focus on other issues involving autism and vaccines but not thimerosal 

– Adjuvants, combination vaccines- other potential etiology for autism 

caused by vaccines that do not contain thimerosal 

• Risk perception research (e.g., level of public concern regarding multiple 

vaccinations) 

Brainstorming Session 2: Adolescent (ages 11 to 18) 

The following were suggested as areas for research or issues of concern: 

• Human papillomavirus (HPV) vaccine use in immunocompromised adolescents 

– May apply to other vaccines (e.g., second dose of varicella vaccine) 

• Immunocompromised hosts 

– Effects of vaccination on disease ( viral load, CD4 counts, etc) 

– Local and systemic unanticipated AEs 

– Replacement serotypes 

– How does immunodeficiency or immunoreactivity affect vaccine dose 

• General issue of special populations in adolescence 

– It may be possible to use existing networks (e.g., for HIV clinical care or 

research) 

• Seek out adolescent minority groups for study 

• Establish baseline rates of neuropsychiatric, rheumatic, and autoimmune disease 

• Need for improved risk-benefit calculations 

• There is a need to look for rare adverse events (especially for vaccines, like 

quadrivalent meningococcal conjugate (Menactra®), that are preventing rare 

diseases) 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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• Studies to rule out spurious associations of vaccines with normal adolescent 

phenomena (e.g., acne, onset of menses) 

• Safety of concomitant vaccines (e.g., quadrivalent meningococcal conjugate, 

tetanus-diphtheria-pertussis (Tdap), and HPV vaccines together or separately) 

• Changes in disease incidence, by gender, in adolescence 

• Establish baseline side-effect profiles of specific vaccine components (e.g., novel 

adjuvant for bivalent HPV) 

• Improved communication regarding expected side effects of vaccines 

Brainstorming Session 3: Adulthood and Pregnancy 

The following were suggested as areas for research or issues of concern: 

• Relevant safety information from passive immunization (e.g., intravenous 

immunoglobulin, Rh-immune globulin) 

• Establish a single national registry for vaccine exposures in pregnancy 

• Better ways to study intended/unintended vaccine exposures during pregnancy 

• Chronic fatigue syndrome as an adverse event (e.g., anthrax vaccine, new 

adjuvanted influenza vaccines) 

• Safety of reimmunization using pneumococcal polysaccharide vaccine 

• Ways to study previously unstudied vaccine combinations 

• “Disability” as an outcome following vaccination 

– Quantify level of disability- include in registry 

• Issues of immunosenescence for zoster vaccine 

– As immunity wanes, potentially increased incidence and increased 

severity of wild type disease: how does vaccine impact? 

• Are current systems adequate to study off-label use? (e.g., Tdap, zoster vaccines) 

– If vaccines are expensive, are they given to people outside of 

recommendations 

– Unintentional/Intentional Off label use 

• Rare adverse events (e.g., vasculitis) following influenza vaccine 

• Travel vaccines—off-label use 

• Travel clinics—potential setting for research 

• Dose response to adjuvants 

• Framework needed to study multiple near-concurrent vaccination 

• “Hyperimmunization” within the Department of Defense 

• ACIP adult guidelines extrapolated from children recommendations? 

– Guidelines based on civilian population that does not receive as many 

vaccines 

• Gender and race considerations, generally 

• Myopericarditis as an outcome following vaccines other than smallpox vaccine 

• Other cardiac adverse events 

• Age-specific considerations within the adult age range 

– Study design considerations 

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Brainstorming Session 4: Vaccine Adjuvants and New Vaccine Technologies 

The following were suggested as areas for research or issues of concern: 

• Subpopulation affects 

• Gender effects 

• Dose response 

• Better definition of baseline reactivity 

• More emphasis on nonclinical studies 

• Difficulty of ascribing causality to specific components of vaccines 

• Better characterization and communication of vaccine components (e.g., by the 

FDA and by the manufacturer), including changes made in vaccine composition, 

over time, by the manufacturer 

• Much research in this area will need to be led and/or conducted by agencies and 

programs outside CDC 

• “Class effect” as a postlicensure surveillance strategy 

• Need to look across age groups 

– Broad age categories an oversimplification 

– Immune response functions in complex ways (e.g., autoimmune functions 

may be affected by age, race, and gender 

– Younger age groups may have more reactive immune systems, while older 

persons’ immune systems may be less reactive? 

• Need to define the adverse events of most interest 

• Formal risk assessments needed for each vaccine component 

• Vectors—“class effects” (e.g., poxvirus for human immunodeficiency virus 

vaccines) 

• How to list vaccine components (e.g., in package insert) in order to be detailed 

but easy to understand? 

• It is possible that 2 vaccines being licensed may never be given together until both 

are licensed, so no information about potential adverse events from the 

combination may be available before licensure 

Discussion and Input from Federal Scientists: Synthesis, Prioritization, and Potential 

Collaboration 

Dr. Snider moderated the discussion. The following points were raised: 

• Strive for balance between “external” (i.e., what the public perceives as 

important) and “internal” safety issues as a focus for research 

• Real-time active surveillance systems (e.g., for pandemic influenza) 

• Linkage among existing registries/immunization information systems to enhance 

real-time surveillance 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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• Establish a national registry and repository to aid in tracking long-latency 

exposures (e.g., simian virus 40) 

– Need for multisite clinical linkages 

• Overcome barriers to research (e.g., remote enrollment) 

• Pandemic influenza integrated into research agenda 

– Identify new projects to be taken on by other agencies 

CDR Broder thanked the participants. She said that the next step would be to incorporate 

the suggestions from today’s meeting and the previous meeting of external consultants 

into the draft research agenda for NVAC’s review. It will be important for the research 

undertaken to provide meaningful information that will enhance public health. 

Closing Remarks—Bruce Gellin 

In his closing remarks, Dr. Gellin stressed the need for readiness across all Department of 

Health and Human Services agencies when the research agenda is finalized in 2008.

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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APPENDIX A: Summary of Brainstorming Session Worksheets 

Overview: 

At the completion of each brainstorming session, participants were asked to complete 

worksheets listing the top 5 vaccine safety research topics in rank order. For each topic, 

participants were also asked to note the reason for importance and identify potential 

approaches to study it. An ISO medical officer reviewed the worksheets and 

summarized the feedback by key research themes. 

Findings:

Forms Returned: 

Fifteen individuals completed forms for at least one of the four sessions. At least one 

scientist from each of the following agencies completed a form for each session: NVPO, 

NIH, FDA, CDC (outside ISO), DoD, and HRSA. Staff from ISO, CDC did not 

complete forms. 

Suggested Research Topics Identified by ≥1 Rater: 

Superscripts are used to show if at least one rater ranked the topic as a first (1) or second 

(2) priority level. Other levels of priority are not shown. 

 

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Session 1: Infants and Children

• Vaccine: 

o Newly licensed vaccines 

o MMR and thrombocytopenia (including genetic risk factors and 

prevention strategies)1

o Rotavirus and intussusception, including genetics2

o MMRV (different than individual MMR and varicella vaccines) 

o Combination vaccines2 

o Pediatric bioterrorism vaccines 

o Pediatric pandemic vaccines (especially with novel adjuvants)2

• Vaccination practices: 

o Multiple vaccines at same visit, including risk for neurodevelopmental 

disorder (also nearly concurrent vaccination)1,2 

o Analysis of medical exemptions for vaccination 

o Off label use of vaccines1

o Clinical guidelines for medical exemptions, outcomes rechallenges1

o Clinical guidelines for adverse event causality assessment2

• Adjuvants and non-antigen components of vaccines 

o Cumulative exposure to proteins (e.g., diphtheria, aluminum) 

o Thimerosal and neurodevelopmental disorders, including those other than 

autism1

o Novel adjuvants: need long-term follow-up1

• Host: 

o Premature, low birth weight2

o Presence of genetic and metabolic conditions 

o Immunocompromising conditions (nephrotic syndrome, HIV) 

o Genetic risk factors1

o Race 

• Reported adverse event following immunization (AEFI) 

o Serious adverse events for newly licensed vaccines1

o Life threatening disorders, including allergic 

o Allergic disease (e.g., wheeze after LAIV)2

o Unexpected death in infancy/ deaths2

o Encephalopathy, including acute disseminated encephalomyelitis (ADEM) 

o Medically attended events after vaccination (case series method)1

o Chronic disease onset long after vaccination 

o Autism and other neurodevelopmental disorders (including other than 

thimerosal-containing vaccines and MMR; assess causes)1

• Risk perception 

o Risk perception and communication (particular around autism) 

o Perception of causality of neural disease in infants through 3 years2

o Reasons for delay in immunization2 

 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Session 1: Infants and Children (continued)

• Other related to vaccine safety research 

o Collect control samples for specimens collected via CISA1

o Background rates for childhood medical events (< 5 years) 

o Is immunization compliance associated with wellness?2 

• Other not related to vaccine safety research 

o Surveillance for serotype replacement for pneumoccocal disease 

o Vaccine effectiveness in low birth weight populations 

Session 2: Adolescents (non-pregnant) Aged 11-18 Years

• Vaccines 

o Newly licensed vaccines1

o HPV, especially new vaccine with novel adjuvant; suggest broad look for 

adverse events; assess risk in persons with chronic conditions, including 

HIV (noted HPV also licensed for girls aged 9 and 10 years)1,2 

o MCV4, especially risk for Guillain-Barre syndrome (GBS)1 

o Tdap 

o Varicella 

o Travel vaccines, including use with regular vaccines 

o Combination vaccine 

• Vaccination practices 

o Simultaneous vaccination1,2

o Vaccination of persons immune (problems with incomplete immunization 

history) 

o Clinical guidelines for medical exemptions, outcomes rechallenges 

o Clinical guidelines for adverse event causality assessment 

• Non-antigen components 

o Diphtheria toxoid (multiple doses), including risk for GBS1

o Adjuvants, especially new adjuvant in HPV (BLA) 

• Host: 

o Gender 

o Immunocompromised, particular for live viral vaccines 

o Chronic conditions (including HIV and immunocompromised – especially 

live vaccines) 

o Genetic risk factors 

o Sports (effect of strenuous exercise on AEFI) 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Session 2: Adolescents (non-pregnant) Aged 11-18 Years

• Reported adverse event following immunization (AEFI) 

o Establish baseline rates for adverse events that could be perceived as 

AEFI1

o GBS and other demyelinating diseases (especially with MCV4, influenza 

vaccine or hepatitis vaccine)2

o Autoimmune diseases 

o Baseline rates for adolescent health conditions, including gynecologic, 

acne, psychiatric, especially with HPV2

o Sexual initiation, especially with HPV1

o Risk perception and communications 

o Overall communication for safety 

• Other not related to vaccine safety research 

o HPV serotype replacement 

o Improve methods for risk benefit assessment, especially for vaccines 

preventing rare diseases 

o Consent issues for adolescents 

Session 3: Adults Aged ≥19 Years and Pregnant Women

• Vaccines 

o Newly licensed vaccines1

o Live vaccine safety in older persons 

o Multiple pneumococcal polysaccharide vaccines; how many doses is it 

safety to receive as an older adult?2 

o Zoster vaccine, including immunosenescence1

o Influenza vaccine and association with neurologic and rare AEFI, other 

than GBS (e.g., vasculitis) 

o Travel and deployment vaccines (e.g., anthrax, smallpox), in conjunction 

with regular vaccines and medications (suggested use of DoD cohort)2

o Influenza vaccine in pregnant women1 

o Tdap vaccine in pregnant women1

• Vaccination practices 

o Simultaneous and near-simultaneous vaccination 

o Off label use of vaccines (e.g., Zoster, Tdap, HPV)1

o Clinical guidelines for medical exemptions, outcomes rechallenges2

o Clinical guidelines for adverse event causality assessment1

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Session 3: Adults Aged ≥19 Years and Pregnant Women (continued)

• Non-antigen components 

o Total adjuvant content received with multiple vaccines; dose response

o Aluminum (exposure from multiple vaccines; component of smallpox and 

Anthrax vaccines)

o Adjuvants - pre-licensure trials need 3 arms to assess safety in adjuvantonly recipients1

o Adjuvants in multiple vaccines and combination vaccines (e.g., role of 

adjuvants and autism)2

o Adjuvant risk in different populations (e.g, across age, race and gender 

groups; autoimmunity in older persons)

o Adjuvants in pandemic and pre-pandemic vaccines

o Effects of cumulative levels of components in vaccines2

o Thimerosal and risk for AEFIs in pregnant women1

• Host: 

o Gender differences for AEFIs, including serious adverse events 

o Interactions with other medications, particularly in older adults1

o Chronic conditions1

o Older age, immunosenescence1,2

o Ethnicity

o Genetic risk factors

o Pregnancy (suggestions for single maternal registry, pregnancy outcome 

database)1,2 

o Increased fetal inflammatory mediators affecting neonatal outcome such 

as low birth weight 

• Reported adverse event following immunization (AEFI) 

o Establish baseline rates for adverse events that could be perceived as 

AEFI, adjusting for gender, race and age 

o Demyelinating diseases1

o Chronic diseases, with onset in older adults2

o Chronic fatigue syndrome2

o Common AEFIs with ranges of severity, including syncope, injection site 

reactions and more severe events

o Disability outcomes

o Autoimmune diseases (e.g., multiple sclerosis, hepatitis) 

o AEFIs in pregnant women (VSD case series) 

• Other related to vaccine safety research

o Live vaccine transmission studies

o Break adult age-group into sub-groups 

o Therapeutic vaccine safety, including cancer vaccines 

• Other not related to vaccine safety research 

o Vaccine immunogenicity studies in the elderly2

o Affect of demographic factors (e.g., ethnicity) on vaccine effectiveness

o Vaccine effectiveness studies in pregnant women

o Elective termination of pregnancy practices after vaccine 

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Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

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Session 4: Vaccine Adjuvants, Other Non-antigen Vaccine Components and New 

Vaccine Technologies

Related topics were also identified during the life-stage sessions, described above. 

• Identify non-antigen components in each vaccine and assess safety profile of 

these components; consider other biological and environmental exposures 

(suggestion that ISO is not the lead) 1

• Association of adjuvants and AEFI (and effectiveness); look at effect of single 

and multiple adjuvants administered once or multiple times1

 

• Cytokine responses to new adjuvants; cell-based safety 1

• Identify potential adverse events in phase 3 trials for which number of subject was 

too small to fully assess risk; ensure information is communicated to ISO1

• Long-term risk of repeated exposure to adjuvant vaccines in older persons, 

particularly for autoimmune diseases2

• Assess if vaccines with same ingredients are associated with similar AEFI2

• Exposure to aluminum in multiple vaccines 

• Cumulative exposures to proteins (e.g., diphtheria toxoid, CRM, tetanus toxoid) 

• Surveillance for adjuvant safety (suggest large surveillance evaluation) 

o Across product classes and age-groups 

o Long-term AEFIs, including cancer (suggest collaboration with NCI 

SEER) 

• Identify specific AEFI of interest for new adjuvant vaccines, by age, gender and 

race; assess background rates 

• Evaluate for cardiotoxicity with novel pox virus vector vaccines 

• Pre-exisiting immunity with recombinant viral vectors and reactogenicity (e.g., 

adenovirus 5) 

• Investigate AEFI (and effectiveness) in sub-populations of older persons to 

determine if additional or fewer doses are needed. 

6
Interagency Vaccine Group Meeting on the Development of CDC’s ISO Scientific 

Agenda – Final 3/21/08 

Appendix B: Abbreviations 

Abbreviation Definition 

ADEM acute disseminated encephalomyelitis 

AEFI adverse event following immunization 

BLA biologics license application 

CDC Centers for Disease Control and Prevention 

CISA Clinical Immunization Safety Assessment Network 

DoD Department of Defense 

FDA Food and Drug Administration 

GBS Guillain-Barre syndrome 

HPV human papillomavirus vaccine 

HRSA Health Resources and Services Administration 

ISO Immunization Safety Office 

LAIV live, attenuated influenza vaccine 

MCV4 meningococcal conjugate vaccine 

MMR measles, mumps and rubella vaccine 

MMRV measles, mumps, rubella and varicella vaccine (combined) 

NCI National Cancer Institute 

NIH National Institutes of Health 

NVPO National Vaccine Program Office 

SEER Surveillance, Epidemiology, and End Results 

Tdap tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine 

VSD Vaccine Safety Datalink 

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