DEPARTMENT OF HEALTH AND HUMAN SERVICES

CENTERS FOR DISEASE CONTROL AND PREVENTION

Advisory Committee on Immunization Practices

October 25-26, 2006

Atlanta, Georgia

Record of the Proceedings

This document has been archived for historical purposes. (11/1/2006)
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 

October 25, 2006

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

HERPES ZOSTER SHINGLES VACCINE............................................................................................. 2 

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

 Epidemiology and Impact of HZ and Postherpetic Neuralgia in Older Adults ................................. 3 

 Results of the SPS........................................................................................................................... 4 

 Review of VZV Economic Studies ................................................................................................... 5 

 Overview of Vaccine Financing by Medicare................................................................................... 6 

 Public Comment Period ................................................................................................................... 8 

 Proposed Recommendations and ACIP Vote on Use of Zoster Vaccine ........................................ 8 

RABIES VACCINE................................................................................................................................ 16

 Overview ........................................................................................................................................ 16

 Review of Human Rabies Prevention in the United States............................................................ 16

 Review of Rabies Biologics............................................................................................................ 17

 Cost-Effectiveness of Rabies PEP................................................................................................. 18

 Proposed Recommendations and ACIP Vote on Rabies PEP and Preexposure Prophylaxis...... 19

CHILD/ADOLESCENT IMMUNIZATION SCHEDULE ......................................................................... 21

 Overview ........................................................................................................................................ 22

 Results of the Immunization Schedule Focus Groups................................................................... 22

 Update on the 2007 Immunization Schedule for Ages 0-18 Years................................................ 23

 ACIP Vote on the 2007 Immunization Schedule for Ages 0-18 Years .......................................... 24

INFLUENZA VACCINE......................................................................................................................... 25

 Overview ........................................................................................................................................ 25

 Update on Cumulative Monthly Influenza Vaccine Distribution ..................................................... 27

 Manufacturer Reports on the Future of Influenza Vaccine ............................................................ 27

 CAIV-T Safety and Efficacy Data................................................................................................... 29

 Public Comment Period ................................................................................................................. 32

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TABLE OF CONTENTS

Page

October 26, 2006

VACCINE FINANCING......................................................................................................................... 34

 Implementation of New Vaccines and Vaccine Recommendations .............................................. 34

 Overview of the NVAC Financing Workgroup................................................................................ 36

Guidance on Use of Zoster Vaccine [continued] .................................................................................. 38

MENINGOCOCCAL VACCINE ............................................................................................................ 39

 Overview ........................................................................................................................................ 39

 Update on the MCV4 Supply ......................................................................................................... 40

 Overview of GBS in MCV4 Recipients........................................................................................... 40

 Decision Analysis of Meningococcal Disease Vaccination in the Presence of GBS ..................... 41

ISO Update ........................................................................................................................................... 43

HPV VACCINE ..................................................................................................................................... 45

 Update on the Quadrivalent HPV Vaccine..................................................................................... 46

 Overview of the GARDASIL® Population Impact Analysis............................................................ 47

 Cost-Effectiveness of a Quadrivalent HPV Vaccine in the United States...................................... 48

Update on the Mumps Outbreak .......................................................................................................... 49

Update on the Vaccine Supply ............................................................................................................. 52

Update on the Global Polio Eradication Initiative ................................................................................. 53

Ex- Officio Reports................................................................................................................................ 56

Public Comment Period........................................................................................................................ 57

Closing Session.................................................................................................................................... 57

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Page A1.1

ATTACHMENT 1 

List of Participants

ACIP Members

Dr. Jon Abramson, Chair

Dr. Ban Mishu Allos

Dr. Carol Baker

Mr. Robert Beck

Dr. Judith Campbell

Dr. Janet Gilsdorf

Dr. Harry Hull

Dr. Susan Lett

Dr. Tracy Lieu

Dr. Julia Morita

Dr. Dale Morse

Dr. Kathleen Neuzil

Ms. Patricia Stinchfield

Dr. Ciro Sumaya

Dr. John Treanor

Dr. Robin Womeodu

Designated Federal Official

Dr. Larry Pickering

ACIP Executive Secretary

Liaison and Ex- Officio Representatives

Dr. Nancy Bennett

National Association of County and City Health 

Officials

Dr. Norman Baylor

Food and Drug Administration

Dr. Joseph Bocchini

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. 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. Steven Gordon

Healthcare Infection Control Practices Advisory 

Committee

Dr. Wayne Hachey

Department of Defense

Dr. Florence Ho

Food and Drug Administration

Dr. Indira Jevaji

Health Resources and Service Administration

Dr. David Johnson

Pharmaceutical Research and Manufacturers of 

America

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

Dr. Monica Naus

Canadian National Advisory Committee on 

Immunization

Dr. Kristin Nichol

Department of Veterans Affairs

Dr. Gregory Poland

American College of Physicians

This document has been archived for historical purposes. (11/1/2006)
Dr. Romeo Rodriquez

National Immunization Council and Child Health 

Program, Mexico

Dr. David Salisbury

London Department of Health

Dr. William Schaffner

National Foundation for Infectious Diseases and

Infectious Diseases Society of America

Dr. Angela Shannon

National Vaccine Program Office

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

Mr. Curtis Allen

Dr. Joseph Bresee

Dr. Angela Calugar

Ms. Annelise Casano-Dickerson

Dr. Bo-Hyun Cho

Dr. Thomas Clark

Dr. Robert Davis

Dr. Gustavo Dayan

Ms. Penina Haber

Dr. Rafael Harpaz

Dr. Robert Keegan

Dr. Susan Manning

Dr. Lauri Markowitz

Dr. Martin Meltzer

Dr. Mark Messonnier

Dr. Nancy Messonnier

Dr. Ismael Ortega-Sanchez

Dr. Umesh Parashar

Dr. Pamela Protzel-Berman

Dr. Lance Rodewald

Dr. Charles Rupprecht

Dr. Anne Schuchat

Ms. Angela Scott

Dr. Jane Seward

Dr. Jean Smith

Dr. Linda Venczel

Dr. Gregory Wallace

Guest Presenters, Press and

Members of the Public

Savant Ahmed

HSBC Securities

Vincent Ahonkhai

GlaxoSmithKline Pharmaceuticals

Jennifer Allen

Merck & Company, Inc.

Shannon Allen

Merck & Company, Inc.

Stephen Allred

Get A Flu Shot.com

Gregory Allsberry

National Autism Recovery Foundation

Karla Allsberry

National Autism Recovery Foundation

Paula Annunziato

Merck & Company, Inc.

Judith Armoni

sanofi pasteur

Jennifer Armstrong

GlaxoSmithKline

Deborah Arrindell

American Social Health Association

Allen Arthur

Slate.com

Phyllis Arthur

Merck & Company, Inc.

Sarah Atanasoff

Health Resources and Services Administration

Kevin Ault

Emory University School of Medicine

Howard Backer

California Department of Health Services

Lynn Bahta

Minnesota Department of Health

Allyn Bandell

MedImmune, Inc.

This document has been archived for historical purposes. (11/1/2006)
Dennis Barnes

GlaxoSmithKline Pharmaceuticals

Eliav Barr

Merck Research Laboratories

Jay Bauman

MedImmune, Inc.

David Beauvais

Generation Rescue

Karen Beauvais

Generation Rescue

Graeme Bell

Merck & Company, Inc.

Soubeyrand Benoit

sanofi pasteur 

Joan Benson

Merck & Company, Inc.

Jeffrey Berg

Wisconsin Department of Health and Family 

Services

Karyn Berry

District of Columbia Department of Health

Kerry Bloch

Moms Against Mercury

Robert Bloch

A-CHAMP

Laura Bono

National Autism Association

Scott Bono

National Autism Association

Donna Bopp

Northeast Health District

Andrew Bowser

AB Writing and Editing, Inc.

Kimberly Bradley

Merck Vaccine Division

Damian Braga

sanofi pasteur

Otis Brawley

Winship Cancer Institute

Nicole Brier

sanofi pasteur

Sandra Brizendine

General Injectables and Vaccines, Inc.

Dennis Brooks

Merck & Company, Inc.

Philip Brunell

National Institutes of Health

Professor Margaret Burgess

National Centre for Immunisation Research

Kimberly Bush

Baxter Healthcare Corporation

Barbie Bushey

Northeast Health District

Jennifer Byrnes

Surveillance Data, Inc.

Keller Carlock

Educating Physicians in Their Communities

Amy Carson

Parent

Ivan Chan

Merck Research Laboratories

Michael Channey

American Academy of Pediatrics

Deborah Charsha-May

MedImmune, Inc.

Peter Chattin

GlaxoSmithKline Pharmaceuticals

Iksung Cho

MedImmune, Inc.

Veronica Chollette

National Cancer Institute

Liana Clark

Merck & Company, Inc.

Lujene Clark

Parent

This document has been archived for historical purposes. (11/1/2006)
Sarah Clark

University of Michigan

Nicole Clarke

Capital Royalty, LP

Richard Clover

University of Louisville

Kathy Coelingh

MedImmune Vaccines

Chris Colwell

Biotechnology Industry Organization

Edward Connor

MedImmune

John Cook

Merck Research Laboratories

Lenore Cooney

Cooney/Waters Group

Rhett Cooper

GlaxoSmithKline Biologicals

Jennifer Corbett

Dow Jones & Co.

Manon Cox

Protein Sciences Corporation

James Cross

Aetna

John Crouch

ASD Solutions

Roberto Cuca

JP Morgan

Joseph DaBronzo

sanofi pasteur

Donald Dalrymple

Dalrymple & Associates, LLC

Adrian Dana

Merck & Co, Inc.

Mike D’Anthony

Sound On-Site, Inc.

Erik Dasbach

Merck Research Laboratories

Allison Davis

Parent

Ana Dayton

Constella Group

Carolyn Deal

National Institute of Allergy and Infectious 

Diseases

Roberto Debbag

sanofi pasteur and National Children’s Hospital

Anna DeBlois

Association of State and Territorial Health 

Officials

Michael Decker

sanofi pasteur and Vanderbilt University

Shelly Deeks

Public Health Agency of Canada

Kenneth Dennison

Wyeth Pharmaceuticals

Sarah Despres

House Government Reform Committee

Shailesh Dewasthaly

Intercell AG

Richard Dinovitz

Wyeth Vaccines

Meg Dorsey

Merck Vaccine Division

Jag Dosanjh

GlaxoSmithKline Pharmaceuticals

Kelley Dougherty

Merck & Company, Inc.

Gary Dubin

GlaxoSmithKline

Jeffrey Duchin

National Association of City and County Health 

Officials

Philippe Duclos

World Health Organization

Colleen Duffy

Merck Vaccine Division

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Laurel Edelman

Surveillance Data, Inc.

Kristen Ehresmann

Minnesota Department of Health

Elamin Elbasha

Merck & Company, Inc.

Jim Evans

Sound On-Site, Inc.

Judith Falloon

National Institute of Allergy and Infectious 

Diseases

Christine Fanelle

Merck & Company, Inc.

Mark Feinberg

Merck Vaccine Division

Tom Fitts

New Hope Center

Jonathan Flacker

Grady Health System

Stephen Ford

Military Vaccine Agency

Serene Forte

MedImmune, Inc.

Wendy Fournier

National Autism Association

Susan Fox

Medical Knowledge Group

Vincent Frascatore

Merck & Company, Inc.

Tammy Freeman

Kennesaw State University

Leonard Friedland

GlaxoSmithKline Biologicals

Marisa Frost

Children’s Healthcare of Atlanta

Sylvina Frutos

GlaxoSmithKline Pharmaceuticals

Sandra Fryhofer

American College of Physicians

Diane Gaffoglio

Nancy Lee & Associates

Susan Garfield

Digene Corporation

Matthew Garrett

Wyeth Vaccines

Diana Gaskins

Georgia Immunization Program

Jeffrey George

TDG, Inc.

Anne Gershon

Columbia University

Ruth Gilmore

Georgia Immunization Program

Steven Goldberg

Constella Group

Karen Goldenthal

Pharmanet Consulting

Daniel Gordon

sanofi pasteur

Mark Gorman

National Coalition for Cancer Survivorship

Elizabeth Goss

Ropes & Gray

Michelle Goveia

Merck & Company, Inc.

John Grabenstein

Merck & Company, Inc.

Cleveland Grady

GlaxoSmithKline

Lisa Guiterman

Ogilvy

Christine Gutekunst

Merck & Company, Inc.

Jill Hackell

Wyeth Vaccines

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Jeffrey Hackman

Emergent BioSolutions

Neal Halsey

Johns Hopkins University

Danielle Halstrom

GlaxoSmithKline Pharmaceuticals

Sandra Hammer

California Department of Health Services

Christopher Haney

Merck & Company, Inc.

Claire Hannan

Association of Immunization Managers

Dionne Hansey

Northeast Health District

Kecia Harris

Merck & Co, Inc.

Alexandra Hauber

Bear Sterns

Richard Haupt

Merck & Company, Inc.

Patti Hawkins

Generation Rescue

Vincent Haynes 

MedImmune, Inc.

Vincent Haynes

MedImmune

Dominic Hein

GlaxoSmithKline Biologicals

Thomas Heineman

GlaxoSmithKline

Curtis Hermann

SciMed

Teresa Hesley

Merck & Company, Inc.

Daniel Hopfensperger

Wisconsin Immunization Program and

Association of Immunization Managers

Jane Horvath

Merck & Company, Inc.

Philip Hosbach

sanofi pasteur

Florence Houn

Food and Drug Administration

Mike Huckman

CNBC

Gina Hunt

Merck & Company, Inc.

Jennifer Huntington

Emergent BioSolutions

Ralph Insinga

Merck & Company, Inc.

Cynthia Jagielski

Sensible Action For Ending Mercury-Induced 

Neurological Disorders (SafeMinds)

Andrea James

Food and Drug Administration

Shirley Jankelevich

South Carolina Department of Health

David Jenkins

GlaxoSmithKline Biologicals

Suzanne Jenkins

National Association of State Public Health 

Veterinarians

Alice Johnson

St. Louis City Department of Health

David Johnson

sanofi Pasteur

Eric Jones

sanofi pasteur

Jim Jones

APCO Worldwide

Hajime Kamiya

Rollins School of Public Health

Niranjan Kanesa-Thasa

Acambis

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Richard Kanowitz

Families Fighting Flu

Brian Katzowitz

Children’s Healthcare of Atlanta

Herbert Kaufman

Louisiana State University Medical School

CmStephen Kay

Generation Rescue

Margaret Keane

Merck Vaccine Division

Sara Keeley

Kennesaw State University

Jeffrey Kelman

Centers for Medicare and Medicaid Services

Paul Kenny

GlaxoSmithKline

Karen Kessnick

Acambis

William Kerry

Parent

Peter Khoury

Baxter Healthcare Corporation

Samuel Kim

Prudential Equity Group, LLC

David Kimberlin 

American Academy of Pediatrics Committee on 

Infectious Diseases

Walter Kimble

Merck & Company, Inc.

Chester Kitchen

Merck & Company, Inc.

Sarah Kobrin

National Cancer Institute

Emma Kofa

National Association of County and City Health 

Officials

Jeffrey Koplan

Emory University

Robert Krakow

Advocates for Children’s Health Affected by 

Mercury Poisoning

Charlotte Kroft

GlaxoSmithKline Pharmaceuticals

Denise Kruzikas

GlaxoSmithKline Pharmaceuticals

Barbara Kuter

Merck & Company, Inc.

Jamie Lacey

MedImmune, Inc.

Scott Laster

Parent

Jennifer Lastinger

Families Fighting Flu

Len Lavenda

sanofi pasteur

Francois Lebel

MedImmune, Inc.

Kay Lee

Generation Rescue

Marie-Michele Leger

American Academy of Physician Assistants

Michelle Lesher

Merck & Company, Inc.

Myron Levin

University of Colorado School of Medicine

Clement Lewin

Acambis

Edward Lewin

MedImmune, Inc.

Julie Liaw

Chicago Department of Public Health

Kai-Li Liaw

Merck Research Laboratories

Patrick Liedtka

Merck & Company, Inc.

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Christopher Loder

Merck & Company, Inc.

Peter Loesher

Merck & Company, Inc.

Christine Long

Center for Community Health

Beverly Lybrand

Merck & Company, Inc.

Peter MacDonald

MedImmune, Inc.

Andrew MacKnight

GlaxoSmithKline Pharmaceuticals

Douglas MacLeod

West Georgia Pediatric Partners

Leonardo Maggi

Universidad de Chile and sanofi Pasteur

Judith Magner

GlaxoSmith Kline

Parthiv Mahadevia

MedImmune

Doris Makari

MedImmune, Inc.

Frank Malinoski

MedImmune

Susan Malone

Coastal Health District 9-1 

Bobbie Manning

Advocates for Children’s Health Affected by 

Mercury Poisoning

Michael Manning

Advocates for Children’s Health Affected by 

Mercury Poisoning

Kyle Margolis

Families Fighting Flu

Patrick Maroney

sanofi pasteur

Cesar Mascarenas-Santos

sanofi pasteur

Dean Mason

Wyeth Vaccines

Kay Mason

Generation Rescue

Marie Mazur

CSL Biotherapies

Robert McDonough

Aetna Insurance Company

Margie McGlynn

Merck & Company, Inc.

Diane McGowan

Families Fighting Flue

Yvonne McHugh

Novartis Pharmaceuticals

Peter McIntyre

National Centre for Immunisation Research

Yves Megard

sanofi pasteur

Lynne Mercedes

Georgia Division of Public Health

Gwen Miller

Massvax Travel Clinic, LLC

John Modlin

Dartmouth-Hitchcock Medical Center

Catherine Moffitt

Vista Health Plans

Glenn Moise

Families Fighting Flu

Julie Moise

Families Fighting Flu

Robeson Moise

Families Fighting Flu

James Moody

Sensible Action For Ending Mercury-Induced 

Neurological Disorders (SafeMinds)

Kelly Moore

Tennessee Department of Health

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Charlotte Moser

Vaccine Education Center at The Children’s 

Hospital of Philadelphia

Linda Moyer

Immunization Action Coalition

Richard Moyer

Public

Barbara Mulach

National Institutes of Health

Martin Myers

National Network for Immunization Information

Karin Nadig

Merck & Company, Inc.

Thomas Netzer

Merck & Company, Inc.

David Neveu

sanofi pasteur

Karen Nielsen

GlaxoSmithKline Pharmaceuticals

Timothy Obara

GlaxoSmithKline Pharmaceuticals

Paul Offit

The Children’s Hospital of Philadelphia

Robert Oliver

Wyeth Pharmaceuticals

Niki Oquist

MedImmune, Inc.

Michael Oxman

University of California-San Diego

Esther Paek

Merck & Company, Inc.

Denise Palmer

Families Fighting Flu

James Pellissier

Merck Research Laboratories

Georges Peter

Brown Medical School

Diane Peterson

Immunization Action Coalition

Stanley Plotkin

sanofi pasteur

Geoffrey Porges

Sanford C. Bernstein & Co., LLC

Keith Powell

Akron Children’s Hospital

Bryan Quattlebaum

California Department of Health Services

Jane Quinn

GlaxoSmithKline Pharmaceuticals

James Ransom

National Association of County and City Health 

Officials

Pamela Rasmussen

Digene Corporation

Mobeen Rathore

University of Florida

Kate Rawson

The RPM Report

Lyn Redwood

Sensible Action for Ending Mercury-Induced 

Neurological Disorders (SafeMinds) 

Stella Reed

Merck & Company, Inc.

Margaret Rennels

GlaxoSmithKline Pharmaceuticals

Elona Rhame

South Carolina Department of Health

Robin Robinett

CSL Biotherapies

Loleta Robinson

MedImmune

Pierrick Rollet

GlaxoSmithKline

Francisco Rosales

Mexico Bioprevencion Inmunization Center

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Paula Rose

GlaxoSmithKline Pharmaceuticals

Brian Rosen

MedImmune

Mitchell Rothholz

American Pharmacists Association

Beth Rowe-West

North Carolina Immunization Branch

Alison Rue

Multnomah County Health Department

Judith Rusk

SLACK, Inc.

Alfred Saah

Merck & Company, Inc.

Thomas Saari

American Academy of Pediatrics Task Force on 

Immunization

Patricia Saddier

Merck Research Laboratories

Alicia Samuels

American Cancer Society

Xenia Sango

CSL Biotherapies

Debbie Saslow

American Cancer Society

Carlos Sattler

Merck & Company, Inc.

William Schaffner

Vanderbilt University Medical Center

David Schechter

Merck & Company, Inc.

Katia Schlienger

Merck & Company, Inc.

Kenneth Schmader

Duke University/Durham Veterans 

Administration Medical Centers

Florian Schödel

Merck Research Laboratories

David Schofield

GlaxoSmithKline Pharmaceuticals

Chris Schott

Banc of America

Lauri Schowalter

GlaxoSmithKline Pharmaceuticals

Anne Schuind

GlaxoSmithKline Pharmaceuticals

Jason Schwartz

University of Pennsylvania Center for Bioethics

Kevin Scotcher

HSBC Securities, Inc.

Laura Scott

Ketchum

Harry Seifert

GlaxoSmithKline Biologicals

Naomi Seiler

House Government Reform Committee Minority 

Staff

Vicki Sharif

Passport Health

Lisa Shaw

Merck & Company, Inc.

Judith Shindman

sanofi pasteur

Indra Sibal

Eternal Horizon

Alan Sievert

American Academy of Pediatrics

Jeffrey Silber

Merck Research Laboratories

Leonard Silverstein

Merck & Company, Inc.

Leah Sirkus

Association of State and Territorial Health 

Officials

Janet Skidmore

Merck & Company, Inc.

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Ben Sloat

Georgia Division of Public Health

Parker Smith

Parker Smith Photography, Inc.

Stephen Smith

sanofi pasteur

Susan Smith

South Carolina Department of Health and 

Environmental Control

Stacie Snodgrass

Merck & Company, Inc.

Stacie Snodgrass

Merck & Company, Inc.

Sandra Snow

Arkansas Department of Health

Paula Soper

National Association of City and County Health 

Officials

Kim Spencer

Generation Rescue

Mary Staat

Cincinnati Children’s Hospital Medical Center

Silvija Staprans

Merck Vaccine Division

Gary Stein

Families Fighting Flu

Robert Steinbrook

New England Journal of Medicine

Corklin Steinhart

Merck & Company, Inc.

Katherine Stone

Public

Raymond Strikas

National Vaccine Program Office

Stacy Stuerke

Merck Vaccine Division

Joseph Sullivan

Merck & Company, Inc.

Ben Sun

National Association of State Public Health 

Veterinarians

Lynne Sweeney

GlaxoSmithKline Pharmaceuticals

Gregg Sylvester

Merck & Company, Inc.

Erich Tauber 

Intercell AG

Anafidelia Tavares

The Balm in Gilead, Inc.

Scott Thigpen

Unify Films

Kirsten Thistle

APCO Worldwide, Inc.

Lonnie Thomas

Henry Schein, Inc.

Michael Thomas

Merck & Company, Inc.

Logan Thornton

National Institutes of Allergy and Infectious 

Diseases

Karen Townsend

American Academy of Pediatrics

Vivienne Treharne

Florida Department of Health Disease Control

Monica Trigg

Georgia Immunization Program

Theodore Tsai

Novartis Pharmaceuticals

Miriam Tucker

Pediatric News

Samuel Turner

Ropes & Gray

James Tursi

GlaxoSmithKline Biologicals

Mark Twyman

MedImmune, Inc.

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William Vecino

TDG, Inc.

Thomas Vernon

Public Health Consultant

Peter Vigliarolo

Cooney Waters

Steven Vignau

Merck & Company, Inc.

John Vittas

Families Fighting Flu

Cara Vivarelli-O’Neill

Merck Vaccine Division

Robert Walker

MedImmune, Inc.

Jean Walters

Merck & Company, Inc.

Tim Wang

UBS Securities

Beth Ward

Georgia Division of Public Health

Beverly Warden

Constella Group

William Waters

Retired Physician

Susan Watkins

sanofi pasteur

Barbara Watson

Philadelphia Department of Public Health

Amanda Welsh

GlaxoSmithKline Pharmaceuticals

Deborah Wexler

Immunization Action Coalition

Julia Whiting

Public

Margaret Williams

APCO Worldwide

Paul Wilson

Intercell, Inc.

Stacey Wilson

Kennesaw State University, Wellstar School of 

Nursing

Amy Wishner

American Academy of Pediatrics

Celia Woodfill

California Department of Health Services

JoAnna Yaksich

Families Fighting Flu

Elizabeth York

GlaxoSmithKline Pharmaceuticals

Laura York

Wyeth Pharmaceuticals

John Zahradnik

sanofi pasteur

Jennifer Zavolinsky

Every Child By Two

Angela Zimm

Bloomberg News

Richard Zimmerman

University of Pittsburgh

Thomas Zink

Emergent BioSolutions

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

AAFP — American Academy of Family Physicians

AAP — American Academy of Pediatrics

ACIP — Advisory Committee on Immunization Practices

AIM — Association of Immunization Managers

AIS — Adenocarcinoma In Situ

ALA — American Lung Association

BLA — Biologics License Application

BOI — Burden of Illness

CAIS — Childhood/Adolescent Immunization Schedule

CAIV-T — Cold-Adapted Influenza Vaccine

CDC — Centers for Disease Control and Prevention

CIN — Cervical Intraephithelial Neoplasia

C. jejuni — Campylobacter jejuni

CMS — Centers for Medicare and Medicaid Services

DSMBs — Data Safety Monitoring Boards

FDA — Food and Drug Administration

FFF — Families Fighting Flu

FQHCs — Federally Qualified Health Centers

GBS — Guillain Barré Syndrome

GMP — Good Manufacturing Practice

GSK — GlaxoSmithKline

HDCV — Human Diploid Cell Vaccine

HepA — Hepatitis A

HepB — Hepatitis B

HHS — Department of Health and Human Services

Hib — Haemophilus influenzae B

HMO — Health Maintenance Organization

HPV — Human Papillomavirus

HRIG — Human Rabies Immune Globulin

HRSA — Health Resources and Services Administration

HUI — Health Utility Index

HZ — Herpes Zoster

IC — Immunocompromised

IDSA — Infectious Disease Society of America

IgG — Immunoglobulin G

IgM — Immunoglobulin M

ILI — Influenza-Like Illness

IOM — Institute of Medicine

ISO — Immunization Safety Office

MCO — Managed Care Organization

MCV4 — Meningococcal Conjugate Vaccine

MMRV — Measles, Mumps, Rubella, Varicella

MMWR — Morbidity and Mortality Weekly Report

mOPV1 — Monovalent Polio Vaccine Type 1

MSW — Medically Significant Wheezing

NCIRD — National Center for Immunization and Respiratory Diseases [proposed]

NCVIA — National Childhood Vaccine Injury Act

NIH — National Institutes of Health

NIS — National Immunization Survey

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NSFG — National Survey of Family Growth

NVAC — National Vaccine Advisory Committee

NVPO — National Vaccine Program Office

P&I — Pneumonia and Influenza

PCECV — Purified Chick Embryo Cell Vaccine

PCV — Pneumococcal Conjugate Vaccine

PEP — Postexposure Prophylaxis

PhRMA — Pharmaceutical Research Manufacturers of America

PSC — Protein Sciences Corporation

QALMs — Quality-Adjusted Life Months

QALYs — Quality-Adjusted Life Years

RCA — Rapid Cycle Analysis

RHCs — Rural Health Centers

sBLA — Supplemental Biologics License Application

SMEs — Subject Matter Experts

SPG — Sucrose Phosphate Glutamate

SPS — Shingles Prevention Study

TIV — Trivalent Inactivated Vaccine

VAERS — Vaccine Adverse Event Reporting System

VFC — Vaccines for Children

VICP — National Vaccine Injury Compensation Program

VNAs — Virus Neutralizing Antibodies

VSD — Vaccine Safety Datalink

VZV — Varicella-Zoster Virus

WHA — World Health Assembly

WHO — World Health Organization

ZE-1 — Zoster Episode 1 

ZE-2 — Zoster Episode 2

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ACIP Meeting Minutes October 25-26, 2006 Page 1 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

CENTERS FOR DISEASE CONTROL AND PREVENTION

ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES

October 25-26, 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 Center for Immunization and Respiratory Diseases (NCIRD) [proposed] 

convened a meeting of the Advisory Committee on Immunization Practices (ACIP). The proceedings 

were held on October 25-26, 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. [Note: the list of 

participants only includes persons who introduced themselves for the record, presented, made public 

comments, or registered prior to the meeting.]

Dr. Jon Abramson, the ACIP Chair, called the meeting to order at 8:03 a.m. on October 25, 2006 and 

welcomed the participants to the proceedings. He particularly recognized the new ACIP members: Drs. 

Carol Baker, Susan Lett, Kathleen Neuzil and Ciro Sumaya. Each new member would serve a four-year 

term from July 1, 2006 to June 30, 2010. Brief backgrounds of the four new ACIP members were 

included in the meeting packets. Dr. Abramson also announced that Dr. Janet Gilsdorf’s term was 

extended for an additional year to complete her ongoing activities as the Human Papillomavirus Vaccine 

(HPV) Workgroup Chair.

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 would be reserved during the meeting for 

public comments, but formal comment periods might also be scheduled during the deliberations of 

specific agenda items. The public was invited to make additional comments during ACIP’s open 

discussions if time permitted. The structure of ACIP meetings would be modified beginning with the 

current meeting to allow for two regularly scheduled updates. The two new presentations would include a 

vaccine safety review and a vaccine supply review of each vaccine recently approved by ACIP.

Dr. Pickering noted the following changes in ACIP representation or participation. Dr. Stanley Grogg, of 

Oklahoma State University, Center for Health Sciences, College of Osteopathic Medicine, would begin 

serving as a new ACIP liaison to the American Osteopathic Association in February 2007. Ex- officio and 

liaison members for the following organizations would be absent from the current meeting: Health 

Resources and Services Administration (HRSA); the National Vaccine Program Office (NVPO); the 

American College of Obstetrics and Gynecology; and the Pharmaceutical Research and Manufacturers of 

America (PhRMA). Replacements for the HRSA ex- officio representative and the NVPO and PhRMA 

liaison members would attend the meeting.

Opening Session

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ACIP Meeting Minutes October 25-26, 2006 Page 2 

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

expertise of a member while serving on ACIP. The following conditions would apply to members with 

limited waivers. First, members who conduct vaccine clinical trials or serve on data safety monitoring 

boards (DSMBs) 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 would not be available or 

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

requested to vote during these circumstances would be asked to disclose any potential conflicts of 

interest.

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

• Dr. Carol Baker serves as an uncompensated member on the Safety Evaluation 

Committee for Merck’s Pediatric Vaccine Programs; received honorarium from sanofi 

pasteur for attendance at an educational conference; received honorarium from 

Inhibitex® for participation on an advisory board; and serves as a consultant to the 

Novartis Group B Streptococcal Vaccine Program.

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

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

• Dr. John Treanor’s institution, the University of Rochester, receives support for clinical 

trials or laboratory studies from Merck, ID Biomedical/GlaxoSmithKline, Protein Sciences, 

sanofi pasteur and AlphaVax. The University of Rochester also has pending support 

from Biocryst.

HERPES ZOSTER (HZ/SHINGLES) VACCINE

The series of presentations, ACIP discussions and votes, and public comments on the shingles vaccine 

are set forth below.

Dr. John Treanor, the Shingles Vaccine Workgroup Chair, reported that the workgroup held about 30 

conference calls following the June 2005 ACIP meeting to review information from CDC and 

manufacturers on economic issues, efficacy, side effects and other outcomes relating to ZOSTAVAX® 

vaccine. A series of presentations would be made and the workgroup’s recommendations would be 

summarized to facilitate ACIP’s discussion and vote on the use of ZOSTAVAX®.

Overview

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Dr. Kenneth Schmader, of Duke University and Durham Veterans Administration Medical Centers, 

presented data on the epidemiology and impact of HZ and PHN in older adults. HZ affects ~1 million 

Americans each year. Data from retrospective case reviews, administrative claims databases and selfreports showed a range in the incidence of HZ of 1.2-4.8 cases/1,000 person-years in adults of all ages 

and 7.2-11.8 cases/1,000 person-years in adults >60 years of age. However, the Shingles Prevention 

Study (SPS) showed an incidence of 11.1 cases/1,000 person-years based on microbiologic confirmation 

of 94% of cases in a cohort of 19,247 adults >60 years of age.

The lifetime risk of HZ has been estimated at 20%-30%. A projection was also made that 50% of persons 

who live until 85 years of age would ultimately develop HZ. The number of HZ cases would be highest in 

immunocompetent older adults and the absolute number of HZ cases would increase as the population 

ages. Several key risk factors for HZ have been identified, including HIV/AIDS, lymphoproliferative 

cancers, organ transplants, systemic lupus erythematosus and immunosuppressive treatment.

Common complications of HZ include acute neuralgia, PHN, ocular complications of ophthalmic zoster, 

scarring and bacterial super-infection. Less common complications of HZ include cutaneous 

dissemination, herpes gangrenosum, pneumonitis, hepatitis, encephalitis, motor neuropathies, myelitis 

and hemiparesis. Of all zoster cases, ~15% involve the ophthalmic division of the trigeminal nerve. 

Without antiviral therapy, 50%-70% of patients with HZ ophthalmicus would develop ocular complications 

that could lead to reduced vision or blindness.

Acute HZ pain is a major cause of significant morbidity in older adults. A prospective study with a cohort 

of 110 patients with HZ found that greater pain burden was associated with increased emotional distress, 

poorer physical or social functioning, and a decreased role. Of the entire cohort, 42% reported acute HZ 

pain as “horrible” or “excruciating,” while 14.6%-26.3% reported acute HZ pain as a barrier to physical or 

social functioning and their roles. A study using SF-36 domains showed that HZ resulted in a lower 

quality of life compared to hypertension, congestive heart failure, diabetes mellitus, myocardial infarction 

and depression.

With respect to PHN, different studies published in the literature have resulted in variable definitions. For 

example, time from rash onset could vary from 30-180 days, while pain intensity could vary from any pain 

to clinically meaningful pain ratings. However, recent definitions focus on any pain 90-120 days after rash 

onset. Despite the differences in definitions, PHN is an exceedingly common cause of neuropathic pain 

that impacts the quality of life of older adults in terms of physical, social, psychological and daily 

functions. The prevalence of PHN has been estimated at 500,000 in the United States and is second 

only to painful diabetic neuropathy or low back pain.

Data from major antiviral trials with cohorts of adults >50 years of age showed that 55% of patients in the 

placebo group had pain 90 days after rash onset, while 25%-35% of patients in the antiviral group had 

pain at this same time point. The SPS showed that the incidence of PHN in the placebo group was 

1.38/1,000 person-years 90 days after rash onset. For purposes of the SPS, “pain” was rated as >3 or 

more on a worst pain scale of 0-10. A strong association was seen between increasing age and the 

prevalence of PHN or duration of pain, but other risk factors that were identified included severity of acute 

pain or rash, painful prodrome and female gender.

Epidemiology and Impact of HZ and Postherpetic Neuralgia (PHN) in Older Adults

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Dr. Michael Oxman, of the University of California-San Diego, reported that the SPS results were 

published in June 2005. In 1998, the Food and Drug Administration (FDA) accepted the SPS protocol 

and primary and secondary endpoints as the principal efficacy study for the investigational zoster vaccine. 

The SPS was designed as a randomized double-blind placebo-controlled trial to test the hypothesis that 

boosting waning varicella zoster virus (VZV)-specific cell mediated immunity in older persons using a live 

attenuated VZV vaccine would protect this population against HZ and PHN. The SPS enrolled and 

actively followed 38,546 subjects >60 years of age at 22 study sites across the United States.

The primary endpoint of the SPS was the “burden of illness (BOI) due to HZ” defined as the sum of HZ 

severity of illness scores in all subjects in the vaccine or placebo group. Subjects who did not develop 

shingles were assigned an HZ severity of illness score of 0. The secondary endpoint of the SPS was the 

“incidence of clinically significant PHN” defined as HZ pain or discomfort with a zoster brief pain inventory 

worst pain score of >3 for more than 90 days after onset of HZ rash. Of 38,546 patients enrolled in the 

study, 41% were female, 46% were >70 years of age, 19,270 were given the zoster vaccine, and 19,276 

were given a placebo. The SPS female population was only 41% due to the small percentage of female 

veterans >60 years of age. More than 95% of patients were followed until the end of the study.

Data collected from the SPA showed the following results. Vaccine recipients did not transmit a vaccine 

virus. The vaccine reduced the BOI due to HZ in the vaccine group by 61.1% compared to the placebo 

group. This decrease represented vaccine efficacy of 65.5% in the younger age strata and 55.4% in the 

older age strata. Both of these outcomes exceeded the pre-specified criteria for “successful” vaccine 

efficacy of a 47% point estimate and a lower bound of the 95% confidence interval of 25%. Data 

presented at a recent Infectious Disease Society of America (IDSA) meeting provided further evidence 

that the HZ BOI would serve as a valid measure of the total adverse impact of zoster on a population of 

older persons. The zoster vaccine was found to reduce HZ pain interference with daily living activities by 

~66%. This measure was similar to the efficacy of zoster vaccine for the HZ BOI.

The SPS also focused on the incidence of PHN and found that vaccine efficacy was 66.5% overall, 65.7% 

in the younger age strata, and 66.8% in the older age strata. For purposes of the SPS, “PHN” was 

defined as significant pain persisting or appearing >90 days after zoster rash onset. Despite this rigorous 

definition, the vaccine was found to reduce PHN by ~66.5%. The SPS provided a low estimate of HZ 

severity and zoster vaccine efficacy. All subjects were seen as soon as possible after HZ rash onset and 

were given state-of-the-art treatment without cost, including Famciclovir and pain management. Of all 

subjects with HZ, 86%-87% received antiviral therapy. Of this subgroup, 64%-66% received treatment 

within 72 hours of rash onset.

Adverse events data collected from >98% of subjects 42 days post-vaccination showed that the 

investigational zoster vaccine was well tolerated. The number of deaths and percentage of subjects with 

>1 serious adverse events were the same in the vaccine and placebo group. The influence of age of the 

subjects on the results was also analyzed in the SPS. Vaccine efficacy for HZ BOI was well maintained in 

the older age strata and over all age groups, undiminished in the incidence of PHN, and significantly 

reduced in the incidence of HZ.

The SPS analyzed severity of illness scores of >600 that represent the equivalent of >2 months in which 

patients reported the “worst imaginable pain” every day. All but one of the subjects 60-69 years of age 

with these severity of illness scores were in the placebo group. Much more severe disease was seen in 

the older age strata. Overall, the zoster vaccine resulted in an 89% decrease of severe cases in subjects 

60-69 years of age and a 68% decrease in subjects >70 years of age for an overall reduction of 73%. 

The vaccine maintained efficacy regardless of the age of the subject. The effect in younger subjects was 

Results of the SPS

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primarily mediated by preventing HZ, while the effect in older subjects was primarily mediated by 

attenuating HZ.

SPS data indicated that vaccine efficacy would be well maintained four years post-vaccination. 

Vaccination of all immunocompetent persons >60 years of age in the United States would result in annual 

reductions of 283,700 HZ cases and 46,400 PHN cases. However, the cumulative impact would be even 

greater due to underestimates of current data. Of >13,000 placebo recipients who have been vaccinated 

to date, none have shown adverse events. Follow-up of a large subset of the originally vaccinated 

subjects is ongoing to analyze zoster rates, examine the same endpoints in the parent study, and 

determine the duration of vaccine persistence.

Several participants provided additional details on the SPS in response to ACIP’s questions and 

comments.

• A recent search showed that only two of 36 adverse events from the zoster vaccine 

reported to the Vaccine Adverse Event Reporting System (VAERS) were serious: 

tachycardia and hospitalization due to zoster one day post-vaccination. Rash, vasal 

dilation and hypersensitivity of injection site were the top three adverse events from the 

zoster vaccine reported to VAERS.

• FDA’s position was that the data were inadequate to support the use of the zoster 

vaccine to treat PHN. As a result, FDA approved an indication for use of the zoster 

vaccine for HZ only.

• A transmission case was reported to Merck, but a specimen has not been obtained to 

date to confirm the case as an oka strain.

Dr. Mark Messonnier, of CDC, summarized data from VZV economic studies. CDC’s literature review 

included one study published in September 2006 and three unpublished studies submitted by CDC and 

two external sources. CDC was aware that another VZV economic study was published in 2001, but this 

research was based on non-U.S. data and was not included in the review.

All four studies considered in the review performed cost-utility analyses and were based on the Markov 

model. Only one of the four studies analyzed adverse events. Three of the studies were conducted from 

a societal perspective, while two of the studies included an additional healthcare perspective. The ages 

of the populations in the four studies ranged from 60+ to 65 years of age.

CDC also reviewed preliminary data from its cost-effectiveness study of vaccinating elderly persons in the 

United States to prevent shingles. The study included outcomes and summary measures for qualityadjusted life years (QALYs), shingles and PHN cases, a cost-utility ratio, number of persons needed to 

vaccinate, and a cost-effectiveness ratio. The study showed that the cost per case of HZ prevented 

would be $3,330; the cost per case of PHN prevented would be $6,405; and the cost per QALY gained 

would be $35,000.

The following ranges were observed in the four external studies: (1) vaccination costs of $149-$200; (2) 

acute HZ costs of $287-$742; (3) HZ incidence rates of 3%-14.29/1,000 person-years based on 

individuals 60-64 years of age or >90 years of age; (4) PHN as a condition of having HZ of 5.1%-32.2%; 

(5) duration of PHN of eight months up to 4.2 years; (6) duration of waning of 9-30 years; and (7) QALY 

weights for PHN of 0.106-0.67. Four studies conducted by CDC and three external sources from a 

societal perspective showed a range in the cost per QALY from $27,000-$112,000.

Review of VZV Economic Studies

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CDC reviewed other vaccine cost-effectiveness data as a basis of comparison with the shingles vaccine. 

The influenza vaccine would result in a QALY of $16,500 for persons 50-64 years of age and costsavings for persons >65 years of age. The meningococcal conjugate vaccine (MCV4) would result in 

QALYs ranging from $138,000-$271,000 for adolescents, toddlers and infants. The second dose of 

varicella would result in a QALY of $96,000. However, CDC acknowledged the difficulty in comparing 

cost-utility analyses between childhood and adult vaccines. As a result, CDC intends to conduct a more 

in-depth mathematical analysis after the studies are published due to differences in methodologies, 

assumptions and measures.

Based on overall results from the studies, the cost-effectiveness ratio would most likely be 

<$100,000/QALY gained. At this time, a rule or “gold standard” has not been established for a non-costsaving intervention to determine an acceptable or unacceptable cost-utility ratio. It is up to decisionmakers to determine whether the value of a QALY would be worth the expenditure of resources.

Dr. Jeffrey Kelman, of the Centers for Medicare and Medicaid Services (CMS), described the strengths 

and limitations in using Medicare for vaccine financing. Medicare Parts A and B cover direct treatment of 

disease. For example, Part B would cover the rabies vaccine after a dog bite, but would not cover the 

vaccine for a Medicare beneficiary who is an animal handler. However, three exceptions to this statute 

were established for the influenza, pneumococcal and hepatitis B vaccines for moderate to high-risk 

persons.

Medicare beneficiaries are not required to pay a deductible or co-payment for influenza and 

pneumococcal vaccines. Physicians who administer any one of the three preventive vaccines are 

allowed to charge current procedural terminology codes under Part B. CMS and HHS extensively 

discussed whether ZOSTAVAX® could be administered under Part B as post-exposure direct treatment. 

However, the agencies realized that a regulatory or statutory change would be needed because the 

existing law could not be interpreted to cover ZOSTAVAX® under Part B.

Medicare Part D covers all FDA-approved drugs defined as “medically necessary” medications. Part D 

includes network drug providers, such as point-of-sale retail, long-term care, home infusion and specialty 

pharmacies. However, Part D excludes specific physicians as in-network providers and does not cover 

vaccines otherwise covered by Part B.

CMS acknowledged that existing statutory language would prohibit coverage of ZOSTAVAX® under 

Medicare Part B. As a result, CMS proposed several strategies to overcome these regulatory barriers 

and pay for ZOSTAVAX® in or out of physicians’ offices. First, the in-network approach would allow 

Medicare beneficiaries to obtain ZOSTAVAX® from point-of-sale pharmacies in 44 states. In addition, 

Part D plans can deliver vaccines to physician offices through in-network specialty distributors. Second, 

the out-of-network approach would allow physicians to obtain ZOSTAVAX® directly from manufacturers, 

administer the vaccine to patients, and charge beneficiaries, who would then submit the bills to the Part D 

plans.

Third, the specialty pharmacy approach would allow Medicare beneficiaries in long-term care and 

assisted living facilities to receive ZOSTAVAX® from long-term care and home infusion pharmacies. 

Several in-network chains are planning to administer ZOSTAVAX® at the point-of-sale, but specialty, 

long-term care and infusion pharmacies would be expected to obtain the appropriate certifications and 

approval from state pharmacy boards before administering the vaccine.

Overview of Vaccine Financing by Medicare

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If ZOSTAVAX® is defined as “medically necessary,” the vaccine would be covered by all Part D plans in 

2007. Physicians could bill Medicare beneficiaries directly for the drug itself as out-of-network and bill 

secondary insurance payers or state Medicaid plans that cover vaccines for cost sharing, but would not 

be allowed to bill an administrative charge for ZOSTAVAX® under Part D. CMS issued guidance 

encouraging the use of all three approaches and strongly emphasized the need for all plans to provide all 

medically necessary treatments and drugs. However, CMS is anxiously awaiting ACIP’s 

recommendations because ZOSTAVAX® will be available in plan year 2006 and in all plans in 2007.

Dr. Kelman was pleased to announce that several activities are underway to promote easier access to 

vaccines. A vaccine-specific web portal was developed to link contracted plans and physicians and 

facilitate electronic billing. A regulation was recently proposed authorizing CMS to link >4 billion Part D 

data elements that are submitted each year. This integrated database, if approved, would link data 

elements from Medicare Parts A and B, hospitals, providers, home healthcare facilities and nursing 

homes in a fully encrypted and longitudinal system.

CMS is confident that the proposed integrated database would serve as a tremendous post-marketing 

surveillance tool for vaccines and all other drugs. Most notably, data will be captured, linked and 

maintained on all 43 million Medicare beneficiaries and vaccine side effects, reactions and efficacy. The 

integrated database will also allow CMS to conduct clinically significant projects with small and defined 

patient subsets.

Dr. Kelman confirmed that he would provide CDC with a written list of questions and answers for both 

healthcare professionals and patients. In the interim, however, he emphasized key points on vaccine 

financing by Medicare that ACIP should consider in formulating its recommendations on the use of 

ZOSTAVAX®. Medicare Part B does not cover any preventive vaccines other than the three exceptions 

defined by statute: influenza, pneumococcal and hepatitis B vaccines. Part D will cover ZOSTAVAX® 

and other large-scale preventive vaccines.

Medicare beneficiaries will pay on average of 25% for ZOSTAVAX® in addition to an administrative fee, 

but three categories of enrollees will be exempt from this requirement. First, dual-eligible beneficiaries 

who receive full benefits from both Medicare and Medicaid will pay $3 for ZOSTAVAX®. Medicaid could 

pay the administrative fee for beneficiaries in this category, but this decision would be made on a stateby-state basis. Second, certain eligible Medicare beneficiaries at 100%-150% of the federal poverty level 

will pay $5 for ZOSTAVAX®. Third, Medicare beneficiaries who receive catastrophic benefits will pay 5% 

for ZOSTAVAX®.

Several ACIP members were pleased with the development of the vaccine-specific web portal to facilitate 

electronic billing and the strategies CMS outlined to promote easier access to vaccines. However, some 

members were extremely concerned about unresolved or unclear issues. Most notably, efforts to 

coordinate Medicare benefits to pay for ZOSTAVAX® will be extremely challenging. Potential problems 

with network pharmacies providing ZOSTAVAX® to providers have not been sufficiently addressed. 

Adequate attention has not been given to payment of the administrative fee to date because beneficiaries 

and employers assume that Medicare would pay its fair share for ZOSTAVAX®. The ACIP members 

strongly urged CMS to clarify these issues for ZOSTAVAX® at this time to avoid facing similar problems 

when other adult vaccines are approved in the future.

Several participants provided additional details on ZOSTAVAX® financing and economic issues in 

response to ACIP’s questions, comments and concerns.

• Merck launched its Vaccine Patient Assistance Program in September 2006 to provide 

ZOSTAVAX® and six other vaccines to uninsured adults with household incomes at or 

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below 200% of the federal poverty level. Physicians’ offices and private clinics can 

administer the seven Merck vaccines to patients who meet these criteria. To avoid 

missed opportunities for vaccination, patients would be allowed to enroll in the program 

and receive a vaccine in the same visit. Merck has initiated dialogue with CDC and other 

key constituents to explore the possibility of expanding the program to public health 

clinics.

• Of the total Medicare Part D population of 22.5 million persons, ~40% or 9.3 million 

qualify for low-income subsidies and would be required to pay a $3 or $5 co-payment. 

However, some health plans intend to use tier 2 formularies to cover ZOSTAVAX®. This 

approach would require beneficiaries to pay a co-payment of $30 or less.

• Merck is pleased that many Medicare Part D plans are considering using the vaccinespecific web portal to coordinate benefits in physicians’ offices at the time a vaccine is 

administered to patients.

• Merck incorporated several studies into its models and also performed a medical record 

review study to investigate a 21-day window prior to stated claimed diagnoses. The 

overall cost-effectiveness ratios were found to be robust regardless of whether this factor 

was included in the models.

Dr. Herbert Kaufman, of the Louisiana State University Medical School, emphasized that HZ causes 

ophthalmic zoster and other significant adverse outcomes in patients. Most notably, daily excruciating 

pain can persist for more than one year, prevent social intercourse and lead to suicide in persons >70 

years of age. Dr. Kaufman urged ACIP to approve the use of ZOSTAVAX® to minimize the incidence of 

this terrible disease.

Dr. William Waters has practiced internal medicine and nephrology for 45 years. He emphasized that 

PHN causes significant depression in older patients due to decreased quality of life. For example, futile 

medications do not adequately resolve pain. Diagnostic resources for shingles are inappropriately 

allocated and lead to unnecessary hospitalizations for abdominal, chest or head pains. Dr. Waters noted 

that prophylaxis with the promising ZOSTAVAX® vaccine would be a much more desirable approach.

Mr. Robert McDonough, of AETNA Insurance Company, announced that AETNA provides coverage for 

ZOSTAVAX® because the vaccine offers important and clinically significant benefits to its members. He 

urged ACIP to also consider the clinically significant benefits of ZOSTAVAX® and approve wide 

availability of the vaccine.

Dr. Rafael Harpaz, of CDC, reported that FDA licensed the zoster vaccine on May 25, 2006 for the 

prevention of HZ in persons >60 years of age. The workgroup made diligent efforts to formulate 

comprehensive guidance to meet the needs of providers and patients. Since September 2005, the 

workgroup has held 30 conference calls to review relevant published and unpublished data on (1) the 

epidemiology and natural history of zoster; (2) zoster vaccine safety, immunogenicity and efficacy; and (3) 

vaccine financing, storage, handling and economic issues.

The workgroup considered and extensively discussed questions on the zoster vaccine submitted to CDC, 

the manufacturer and in response to a survey. The workgroup proposed recommendations based on 

Public Comment Period

Proposed Recommendations and ACIP Vote on Use of Zoster Vaccine

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expert opinion when data were inadequate and presented its preliminary guidance to ACIP during the 

June 2006 meeting. The workgroup also asked practitioners to review the proposed recommendations to 

ensure that clinical needs would be met.

The workgroup acknowledged that ACIP’s efforts to provide guidance for specific clinical settings even 

with incomplete evidence are different than FDA’s function. As a result, the workgroup attempted to 

formulate “off-label” guidance that could rapidly yield data and would be consistent with the label 

whenever possible and appropriate. However, the workgroup also realized that off-label guidance might 

dissuade studies on defining vaccine safety and efficacy. Moreover, benefits for studies and the overall 

regulatory process might be delayed and FDA might provide narrow indications. Overall, the workgroup 

agreed that off-label guidance should be given judiciously and only in select settings where vaccine safety 

and efficacy would be likely.

Dr. Harpaz presented the workgroup’s proposed recommendations for the use of ZOSTAVAX®. The 

issues being brought to a vote were selected based on (1) size of the impacted population; (2) degree of 

the workgroup’s discussion; (3) consistency with the package label; and (4) the absence of relevant 

guidance from existing ACIP statements. He also summarized issues the workgroup considered in 

support of or against each policy.

Vote 1: “ACIP recommends that adults 60 years and older receive a single dose of zoster vaccine.” 

Considerations against this policy are as follows. The burden of disease is pain and would be borne by 

an adult rather than a child. Effects on a population would be limited. Decisions could be made from a 

doctor/patient perspective rather than a public policy perspective. Severe disease or death would not be 

common in immunocompetent persons. The disease would not result in a significant amount of lost work 

time due to the primary target population of retirees. Results from economic analyses have shown 

variations in dollars/QALY by factors of four and also demonstrated strong sensitivity to analytic 

approaches, types of models and parameter values. Empiric or theoretical consensus is lacking for 

several key economic issues. The vaccine appears to be expensive.

Considerations in support of this policy are as follows. The burden of disease is substantial and can 

shatter lives due to depression or suicide. The vaccine is safe and fairly effective. Both providers and 

patients have expressed an interest in the vaccine. Weak support from ACIP could lead to modest 

financing by Medicare, private insurers and the VA as well as disparities in poor and vulnerable 

populations. The disease could result in a significant amount of lost leisure time among the primary 

target population of retirees. Economic analyses have demonstrated that the vaccine is within the 

acceptable range of cost-effectiveness.

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

adults >60 years of age. A motion was properly placed on the floor and seconded by Dr. Hull and Ms. 

Stinchfield, respectively. ACIP passed the motion by a majority vote:

• 13 in favor: Abramson, Allos, Beck, Gilsdorf, Hull, Lett, Lieu, Morita, Morse, Neuzil, 

Stinchfield, Sumaya, Womeodu.

• 2 abstentions: Baker, Treanor.

• 0 opposed.

Vote 2: “ACIP recognizes that it is quite plausible that zoster vaccine is safe and effective in persons 

under 60 years of age. However, in the absence of adequate data on safety and efficacy for this 

population and in the absence of an FDA license, ACIP does not routinely recommend the vaccine for 

persons under 60 years of age.” The workgroup considered the following issues in proposing this 

recommendation. Based on considerations of safety and benefit, the manufacturer requested a 

ZOSTAVAX® license from FDA for persons 50-59 years of age in addition to those >60 years of age who 

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were studied in the vaccine trial. Both patients and physicians expressed an interest in the shingles 

vaccines for persons <60 years of age. The workgroup is interested in providing explicit guidance for this 

common clinical issue.

Considerations in favor of a policy that would extend use of zoster vaccine to persons <60 years of age 

are as follows. Increased vaccine efficacy with decreasing age observed in the zoster trial suggested 

efficacy in persons <60 years of age. The association between a decrease in the relative risk of adverse 

events and decreasing age observed in the zoster trial indicated solid vaccine safety in persons <60 

years of age.

The burden of zoster is substantial in persons <60 years of age. National disease rates show that 

~180,000 persons 50-59 years of age are affected by zoster each year and 9,000-22,000 persons in the 

same population are impacted PHN each year. The burden of disease would result in lost work because 

70% of the population is employed. Other persons <60 years of age might be especially vulnerable to 

PHN or shingles, including individuals with depression, pre-existing chronic pain, poor pain tolerance or 

certain occupations.

Considerations against a policy that would extend use of zoster vaccine to persons <60 years of age are 

as follows. For persons <60 years of age, limited data have been collected on vaccine safety and 

immunogenicity and no vaccine efficacy data have been gathered. The risk of PHN would be low in 

persons <60 years of age. No evidence has been produced to support the concern that the prevention of 

reactivation of disease in vaccinated persons <60 years of age might shift the risk of zoster to later ages 

when more PHN would be present. However, persons 50-59 years of age represent a very large cohort 

of ~37 million, and routine vaccination might be inappropriate for such a broad age-based cohort without 

a supporting FDA license. Even in the absence of specific FDA approval for use of vaccine in persons 

<60 years of age, physicians always have the option to offer the vaccine to patients off-label.

Dr. Abramson called for a motion on the proposed recommendation for no routine zoster vaccination of 

adults <60 years of age. A motion was properly placed on the floor and seconded by Drs. Beck and 

Neuzil, respectively. Several ACIP members made comments and suggestions to clarify and refine the 

language.

• The language should be revised to be positive rather than negative. Physicians will most 

likely only read the last sentence of the recommendation and interpret the guidance to 

mean that ACIP actively discourages vaccination for persons <60 years of age.

• The language should be changed to “ACIP does not recommend routine vaccination for 

persons under 60 years of age.”

• More science-based evidence on vaccine safety and efficacy should be gathered to 

support the recommendation.

• The following new language should be added at the end of the recommendation: “In 

certain circumstances, however, physician judgement may warrant vaccination.”

• “Absence of an FDA license” should be deleted from the recommendation.

• The recommendation should be revised to clarify that “ACIP does not recommend routine 

vaccination for persons <60 years of age at this time.”

Dr. Abramson noted that ACIP agreed with the overall sense of the recommendation for no routine zoster 

vaccination of adults <60 years of age, but the voting members did not reach consensus on specific 

wording changes. As a result, he asked the members to submit revisions to Drs. Harpaz or Treanor.

ACIP passed the motion by a majority vote with the condition that Drs. Harpaz and Treanor would 

revise the language based on comments submitted by the members:

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ACIP Meeting Minutes October 25-26, 2006 Page 11

• 13 in favor: Abramson, Allos, Beck, Gilsdorf, Hull, Lett, Lieu, Morita, Morse, Neuzil, 

Stinchfield, Sumaya, Womeodu.

• 2 abstentions: Baker, Treanor.

• 0 opposed.

Vote 3: “ACIP recommends zoster vaccine for persons >60 years of age whether or not they report a 

prior episode of zoster. It would seem the benefit of vaccination may be limited soon after the prior 

episode, though data do not allow establishment of a threshold of time before which benefits do not 

warrant vaccination.

Considerations in making this determination of when to vaccinate would include reliability of the zoster 

history, pain and disability from that episode and any factors that would make the patient particularly 

vulnerable to a recurrent episode. It is not necessary to specifically ask patients about history of zoster 

before offering them the vaccine.” The workgroup considered the following issues in proposing this 

recommendation. Prior history of zoster is listed in the package label as a precaution to zoster 

vaccination with the following statement: “The use of ZOSTAVAX® in individuals with a previous history 

of zoster has not been studied.”

Considerations against this policy are as follows. Approximately 15% of persons will have had a prior 

episode of zoster by the age of 60, but the percentage would be higher in the entire population of persons 

>60 years of age. The vaccine is not licensed for persons with prior zoster. The initial rate and severity 

of zoster episode 2 (ZE-2) after zoster episode 1 (ZE-1) is unknown, but would appear to be diminished. 

No safety or efficacy data have been collected on vaccination of adults with prior zoster.

Considerations in support of this policy are as follows. A 10%-20% error rate has been estimated in the 

reported history of zoster. Self-diagnosis is questionable, while remote diagnosis might lead to recalls in 

the target population. A solid methodology has not been developed to confirm zoster history. These 

uncertainties could result in a burden to physicians and additional barriers to vaccination.

The rate of ZE-2 is not well defined, but appears to be similar to the risk of ZE-1 on an annual basis. 

Persons with ZE-1 might be predisposed to ZE-2. Confirmed cases in healthy adults have been 

documented to occur within one to two years in the shingles trial. No factors have been identified to 

support concerns about vaccine safety. The vaccine would most likely add protection, particularly if a 

history of zoster is remote.

Dr. Abramson called for a motion on the proposed recommendation for persons regarding prior zoster 

episodes. A motion was properly placed on the floor and seconded by Drs. Gilsdorf and Hull, 

respectively, to amend the recommendation as follows: “ACIP recommends zoster vaccine for persons 

>60 years of age whether or not they report a prior episode of zoster. A history of herpes zoster should 

not influence the decision to offer zoster vaccine.”

ACIP passed the amended recommendation by a majority vote:

• 13 in favor: Abramson, Allos, Beck, Gilsdorf, Hull, Lett, Lieu, Morita, Morse, Neuzil, 

Stinchfield, Sumaya, Womeodu.

• 2 abstentions: Baker, Treanor.

• 0 opposed.

Vote 4: “Vaccination with a single dose of zoster vaccine should be considered in limited clinical 

circumstances in which an immunocompetent person of any age with a verified history of varicella is 

anticipated to become immunocompetent due to progression of his or her specific medical condition or 

specific medical treatments.” “Verified history” would require IgG testing with conventional and 

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ACIP Meeting Minutes October 25-26, 2006 Page 12

commercially available laboratory testing in persons <60 years of age, but testing would not be required 

for persons >60 years of age.

The workgroup considered the following issues in proposing this recommendation. Many situations occur 

in which immunocompromised (IC) can be anticipated, including chemotherapy or radiation therapy for 

solid tumors; organ transplantation for failure of kidneys and other organs; and administration of IC 

agents for inflammatory conditions, such as rheumatoid arthritis, lupus, Crohn’s and psoriasis. The 

period of time until IC is expected to occur can vary in these situations from days to years. The number of 

persons anticipating IC is increasing due to an increasing number of indications for IC and also due to 

better and more intensive treatments. An informal evaluation suggests that at least five million persons 

are in situations in which they can anticipate IC; most of these persons are <60 years of age.

The magnitude of risk of zoster introduced by IC is typically much greater than that introduced by age. 

For example, the rate in solid organ transplant recipients is ~10 times higher in IC persons compared to 

the general population, whereas the rate in persons >60 years of age is only two times higher compared 

to persons 50-59 years of age. The risk of the most severe complications of zoster, including 

dissemination, neurologic and ophthalmic disease and death, is increased to an even greater degree as 

compared to age alone.

The workgroup’s position is that the risk of zoster vaccination in immunocompetent persons anticipating 

IC is not increased. Indeed, the risk of zoster vaccination in persons with a history of chickenpox and 

thus at risk of zoster is very likely not increased even in persons who are currently IC since they appear to 

retain effective specific immunity against VZV. For example, repeated episodes of chickenpox (caused 

by wild-type VZV) are rare and generally not severe in IC persons. Also, clinical trials have demonstrated 

that varicella vaccine was well tolerated in IC patients even without a prior varicella history, including 

those with leukemia in remission and HIV-positive persons with CD4 counts >15%. Finally, antiviral drugs 

remain an option to treat disseminated attenuated VZV should this very unlikely outcome occur.

Three studies have shown the benefits of zoster vaccination in IC persons. Live or heat inactive 

attenuated VZV in three different regimens was found to prevent or mitigate zoster in severely IC patients, 

including persons with leukemia in remission and recent bone marrow or stem cell transplant recipients. 

These studies provided a proof-of-concept that demonstrated even profoundly IC persons could in theory 

be protected from zoster with immunoprophylaxis. Most vaccines prevent disease by preventing 

infections; therefore, IC persons can avoid attenuated vaccines with other strategies to limit exposure. 

However, almost all older adults harbor VZV. IC rather than exposure is the key risk factor for VZV 

reactivation. No practical prevention tool has been developed to date other than vaccine.

The zoster vaccine provides no benefit in terms of zoster prevention in persons with no latent VZV or 

varicella history. Zoster vaccine is safe, but is more likely to replicate as a live vaccine and cause 

adverse reactions in persons with no varicella history or specific immunity to VZV. Therefore, laboratory 

confirmation of VZV history would be needed for IC persons who are less able to control replication of 

attenuated VZV in the absence of specific immunity, and who are younger than 60 years of age and thus 

more likely to have a false-positive history of varicella.

Considerations against this policy are as follows. Limited or no actual data are available on vaccine 

safety, efficacy and immunogenicity in immunocompetent persons anticipating to be IC. A post-hoc 

analysis of a small number of subjects who became IC during the SPS did not demonstrate efficacy 

between zoster and pain. The vaccine is not licensed for immunocompetent persons <60 years of age 

who anticipate becoming IC.

Considerations in support of this policy are as follows. Vaccine safety and immunogenicity should be 

completely unaffected prior to IC. Effectiveness should be retained upon IC based on efficacy of (1) live 

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VZV versus varicella prior to organ transplantation; (2) live VZV versus varicella in currently IC persons; 

and (3) a live VZV vaccine or a heat-inactived VZV vaccine, versus zoster in currently IC persons. 

Regarding the post-hoc analysis of SPS data suggesting lack of efficacy, the study was not designed to 

precisely assess this group or evaluate the risk of severe complications.

The vaccine is licensed for immunocompetent persons >60 regardless of anticipated immunocompromise 

and the safety profile should be no different for persons <60 at risk for zoster. Providers are seeking 

guidance on common and important clinical scenarios. As a result, permissive language should be 

developed for a narrow clinical indication with uncertainties highlighted in the background. The potential 

for safely reducing disease burden is large in light of the risk of zoster and its severe complications in this 

group.

Dr. Abramson opened the floor for comments on the proposed recommendation. Suggestions by the 

ACIP members and other participants to clarify and refine the language are outlined below.

• ACIP should decide whether to address or remain silent on lower age limits or leave this 

decision to the discretion of physicians.

• The option of incorporating an age cutoff into the recommendation, such as 18 or 20 

years of age, should be explored because vaccine safety would be less of a concern in 

this population.

• The language should be changed to emphasize a “serologically verified history of 

varicella disease.”

• The routine vaccine safety surveillance system should be designed to follow and monitor 

vaccine adverse events in the target population.

• Caution should be taken in approving the recommendation due to limited or no vaccine 

safety and efficacy data in IC populations. ACIP should collect solid data and approve 

the recommendation at a later time with supporting evidence is available.

• The language should be changed to “may be considered” to acknowledge the lack of 

evidence.

• The two vaccines should be compared if the incidence of zoster is expected to be high in 

IC children.

• The recommendation should be revised to include a specific timeline on the length of 

time a patient would be expected to become IC.

• The recommendation should be changed to explicitly state that data are not available for 

these age groups. Decision-making should be left to the discretion of providers with 

experience in treating these populations.

• The language should emphasize the need for studies in the IC population.

Dr. Abramson called for a motion on the proposed recommendation for vaccination of IC persons. A 

motion was properly placed on the floor and seconded by Drs. Gilsdorf and Lieu, respectively, to amend 

the recommendation as follows: “Vaccination with a single dose of zoster vaccine may be considered in 

limited clinical circumstances in which an immunocompetent person of any age with serological evidence 

of immunity and no documentation of varicella vaccination is anticipated to become immunocompetent 

due to progression of his or her specific medical condition or specific medical treatments.”

ACIP did not pass the amended recommendation:

• 5 in favor: Gilsdorf, Hull, Lett, Lieu, Morita.

• 8 opposed: Abramson, Allos, Beck, Morse, Neuzil, Stinchfield, Sumaya, Womeodu.

• 2 abstentions: Baker, Treanor.

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ACIP Meeting Minutes October 25-26, 2006 Page 14

Vote 5: “Vaccination with a single dose of zoster vaccine should be considered for persons infected with 

HIV with a verified history of varicella. Consideration should extend to persons with CD4 counts >200 

mm3 and/or >15% of total lymphocytes regardless of prior course of their HIV disease so long as these 

values have been present for >3 months and that they have been on stable antiretroviral therapy for >3 

months. While ZOSTAVAX® is licensed for persons >60 years of age, the rationale for considering 

vaccination of persons infected with HIV extends to persons of any age with a history of varicella.”

The workgroup considered the following issues in proposing this recommendation. The label lists “AIDS 

or other clinical manifestations of infection with HIV” as contraindications for ZOSTAVAX®. However, 

these conditions do not cover HIV-infected persons with less advanced disease, such as HIV-positive 

persons without AIDS or clinical manifestations. Persons diagnosed with AIDS remain in this status 

regardless of current clinical status or CD4 counts, but this status does not reflect the biology or current 

medical management of HIV disease.

The risk and severity of zoster varies inversely with CD4 count and depends on duration of HIV infection 

and on antiviral treatment. The age-specific rate in HIV-infected persons is >10-fold higher compared to 

the general population. HIV-positive persons experience various severe complications of shingles. 

Safety, immunogenicity and efficacy of the zoster vaccine are likely to vary by the status of HIV infection.

Considerations against this policy are as follows. No safety data have been collected and no efficacy 

studies have been conducted on zoster vaccine in HIV-positive patients. Considerations in support of this 

policy are as follows. Trial data have demonstrated the safety of the varicella vaccine in HIV-positive 

patients with a history of varicella. The varicella vaccine is safe in VZV-susceptible IC and HIV-positive 

patients with CD4 counts >15%.

ACIP now recommends consideration of varicella vaccine in HIV-infected children and adults with CD4 

counts >15% or >200. Use of zoster vaccine in such persons should only be safer since they would have 

pre-existing specific immunity to VZV. No recurrent varicella has been observed in HIV-positive patients. 

Antiviral drugs serve as additional insurance in this population. Evidence has shown that various vaccine 

regimens can protect even highly IC persons compared to zoster.

Dr. Abramson opened the floor for comments on the proposed recommendation. Suggestions by the 

ACIP members and other participants to clarify and refine the language are outlined below.

• The requirement in the recommendation for persons to be on stable antiretroviral therapy 

for >3 months to receive the vaccine should be clarified. Many HIV patients with CD4 

counts of >200 or >500 have no indication for antiretroviral therapy. For example, 

initiation of antiretroviral therapy would be inappropriate for an HIV patient with a CD4 

count of 700 who is regularly seen by a physician.

• The language should be consistent with ACIP’s previous decision not to recommend the 

measles, mumps and rubella vaccine (MMRV) for HIV-positive children. ACIP’s decision 

was partly driven by the lack of evidence on use of MMRV in this population.

• ACIP should take caution in approving the recommendation due to the absence of data 

and should should call for additional studies in this area. Most notably, Merck is 

conducting a study on ZOSTAVAX® in persons with HIV and well preserved immune 

functions.

Dr. Abramson did not call for a formal motion on the recommendation. ACIP supported Dr. Abramson’s 

proposal to revise the text to emphasize the need for additional studies on vaccination of persons with 

less-advanced HIV disease.

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Vote 6: “There is a precaution regarding use of zoster vaccine in the following persons except as noted. 

Ultimately, the physician must assume responsibility for assessing the immune status of his/her patient 

based on clinical and laboratory evaluation.” The list of persons is included in the section entitled 

“precaution for use of zoster vaccine among immunocompromised persons.” The recommendation also 

lists eight categories where persons should not receive zoster vaccine. This language was extracted 

from other ACIP statements and general recommendations.

The workgroup considered the following issues in proposing this recommendation. The package label 

lists the following contraindications for ZOSTAVAX® and notes that the vaccine should not be 

administered to (1) individuals with a history of primary or acquired immunodeficiency states, including 

leukemia; lymphomas of any type or other malignant neoplasms affecting the bone marrow or lymphatic 

system; or AIDS or other clinical manifestations of infection with HIV; and (2) individuals on 

immunosuppressive therapy, including high-dose corticosteroids. ACIP previously developed and 

approved explicit language to clearly define contradictions and precautions to vaccination. The language

is posted on the CDC web site and was reviewed by the workgroup.

Zoster vaccine is the only live-attenuated vaccine licensed for potential routine use by older persons. The 

portion of older IC persons is much higher than IC children and younger adults. The spectrum of IC 

treatments and conditions is much more varied in older persons. Physicians need guidance on the use of 

zoster vaccine in IC persons due to the burden of zoster in this population. Measles, polio and other 

vaccine-preventable diseases are severe in IC persons, but this population is also at risk of adverse 

reactions to live vaccines and are less likely to respond.

Vaccination of IC persons with live vaccines would involve careful consideration of risks and benefits. A 

review of risks and benefits is also appropriate for ZOSTAVAX®, but this vaccine is different than other 

live vaccines and requires decisions to be shifted toward consideration of IC persons. These factors 

include lack of alternative prevention strategies, high burden of disease, potential for vaccine 

effectiveness, and evidence of acceptable risks in IC persons.

Dr. Abramson opened the floor for comments on the proposed recommendation. Suggestions by the 

ACIP members and other participants to clarify and refine the language are outlined below.

• ACIP should not approve the recommendation because the precautions are in direct 

opposition to contraindications listed on the package label. As an advisory body to CDC, 

ACIP should not issue guidance that conflicts with recommendations by another HHS 

agency. FDA would strongly object to this recommendation.

• Language should be incorporated into the contraindications section to reiterate standards 

for live viral vaccines for IC persons.

• The following language should be deleted from the recommendation: “Ultimately, the 

physician must assume responsibility for assessing the immune status of the patient.” 

New text should be incorporated as follows: “These contraindications are listed in the 

product insert. However, any decision to vaccinate would be based on the provider’s 

assessment of the degree of immunocompromised and discussions with the patient 

about potential risks and benefits.”

Dr. Abramson did not call for a motion on the proposed recommendation for precautions for IC persons. 

ACIP supported the approach suggested Dr. Anne Schuchat of CDC. The statement would contain a 

section to reiterate the label contraindications, but this language would not be included in the 

recommendation.

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ACIP Meeting Minutes October 25-26, 2006 Page 16

RABIES VACCINE

The series of presentations and ACIP’s discussion and vote on the rabies vaccine are set forth below.

Dr. Harry Hull, the Rabies Workgroup Chair, announced that the workgroup was formed in August 2005 

with diverse representation from ACIP, CDC and professional organizations. The workgroup solicited 

input from industry and state and local public health practitioners; held monthly conference calls to review 

the evidence; and communicated frequently to revise the recommendations.

The workgroup was charged with conducting the following activities. ACIP’s 1999 recommendations on 

human rabies prevention would be revised to reflect the current status of rabies epidemiology and antirabies biologics. Information on human and animal rabies epidemiology would be updated. Evidence on 

the efficacy, effectiveness, immunogenicity and safety of anti-rabies biologics would be summarized. The 

cost-effectiveness of rabies postexposure prophylaxis would be assessed. The proposed 

recommendations for rabies preexposure and postexposure prophylaxis (PEP) would be presented to 

ACIP for a formal vote. During the current meeting, a series of presentations would be made to facilitate 

ACIP’s discussion and vote on the workgroup’s recommendations for rabies preexposure prophylaxis and 

PEP. 

Dr. Charles Rupprecht, of CDC, reported that rabies is an acute and progressive encephalomyelitis with 

the highest case fatality rate of any infectious disease. To date, 11 known species or genotypes that 

cause rabies have been identified. The incubation period is typically several weeks to months, but could 

range from days to years. The United States experienced a marked decrease in rabies cases from 

domestic animals after World War II and is the most recent country to become canine rabies-free. A 

decreasing trend in rabies cases among both dogs and cats has been seen. The likelihood of human 

exposure to a rabid domestic animal in the United States has declined. None of the eight human rabies 

cases reported in 2004 were acquired from indigenous domestic animals.

Wild animals are the most important potential source of rabies infection for humans and domestic 

animals. Most reported cases occur in carnivores and bats. Nearly all human rabies cases in recent 

years were caused by variants associated with bats. Of 11 human rabies cases reported in 2004-2006, 

five were attributed to bat exposure. Of the remaining six cases reported in 2004, two were caused by 

canine rabies infections acquired outside the United States and four were caused by transplantation of 

organs and vascular tissue from a deceased patient.

Each year, ~16,000-39,000 potentially exposed persons receive post-exposure prophylaxis. The United 

States has faced intermittent shortages of rabies biologics in recent years. The current biologics are safe, 

but prophylaxis is occasionally complicated by minor adverse reactions that are rarely severe. Clear and 

specific recommendations regarding appropriate preexposure and postexposure rabies vaccination are 

critical to reduce inappropriate prophylaxis and maximize prophylaxis when necessary.

Overview

Review of Human Rabies Prevention in the United States

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ACIP Meeting Minutes October 25-26, 2006 Page 17

Dr. Susan Manning, of CDC, reported that three cell culture rabies vaccines are licensed for use in the 

United States. The rabies vaccine adsorbed is no longer available. The human diploid cell vaccine 

(HDCV) is manufactured by sanofi pasteur, prepared from the Pitman Moore strain, and grown on MRC 

human diploid cells. HDCV is concentrated by ultra-filtration and inactivated with beta-propriolactone. 

HDCV is formulated for intramuscular administration in a single-dose vial containing lyophilized vaccine 

and reconstituted with sterile diluent to a final volume of 1 mL prior to administration. The potency of 

each dose is >2.5 IU/mL of rabies virus antigen. Intradermal HDCV is no longer available in the United 

States.

The purified chick embryo cell vaccine (PCECV) is manufactured by Novartis, prepared from the fixed 

rabies virus strain Flury LEP, and grown in primary culture of chicken fibroblasts. PCECV is inactivated 

with beta-propriolactone and processed by zonal centrifugation. PCECV is formulated for intramuscular 

administration in a single-dose vial containing lyophilized vaccine and reconstituted with sterile diluent to 

a final volume of 1 mL prior to administration. The potency of each dose is >2.5 IU/mL of rabies virus 

antigen.

Two human rabies immune globulin (HRIG) preparations are licensed for use in the United States. 

HyperRabTM S/D is manufactured by Talecris Biotherapeutics and Imogam® Rabies-HT is manufactured 

by sanofi pasteur. Both HRIG preparations are prepared by cold ethanol fractionation of hyperimmunized donor plasma and are standardized at an average potency of 150 IU/mL. The recommended 

dose is 20 IU/kg body weight. Both HRIG preparations are equally efficacious when used as 

recommended.

Randomized controlled human trials and cohort studies with untreated comparison groups would provide 

the best evidence of the effectiveness and efficacy of rabies PEP. However, no controlled studies with 

unvaccinated groups have been conducted due to nearly universal fatality of human rabies cases. To 

evaluate PEP effectiveness and efficacy, the workgroup reviewed the available literature, including 

immunogenicity studies, direct evidence from field experiences with humans exposed to rabies, and direct 

evidence from controlled animal studies. Key outcomes from the literature review are outlined below.

Three studies published in 1923, 1954 and 1987 demonstrated a substantial protective effect of rabies 

vaccination. Multiple published studies showed that the cell-culture rabies vaccine plus HRIG was 

effective in preventing human rabies. Two studies published in 1955 and 1988 showed the importance of 

RIG administration in conjunction with vaccine. A study published in 1971 demonstrated that anti-rabies 

serum alone resulted in poor protection from rabies in rhesus monkeys.

Assessments of protective immunity of the rabies vaccine are complex. Virus neutralizing antibodies 

(VNAs) are believed to have a primary role, but other immunologic factors are important as well. 

Although definitive protective titers cannot be described, two working definitions of adequate rabies VNA 

reference values have been developed to define an appropriate intact host response: (1) antibody titer 

>0.5 IU/mL, used by the World Health Organization (WHO) as an indicator or an adaptive immune 

response and (2) complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focused 

inhibition test, used by ACIP as an indicator of an adaptive immune response. Several published studies 

demonstrated the ability of rabies PEP, including a combination of cell-culture vaccine and HRIG to 

produce VNA >0.5 IU/mL by day 14.

Direct evidence of preexposure prophylaxis in protecting against rabies is unavailable. Animal models 

have shown that primary immunization with HDCV or PCECV provides protection from a productive 

rabies infection after virus challenge. Multiple studies have demonstrated that three intramuscular doses 

Review of Rabies Biologics

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ACIP Meeting Minutes October 25-26, 2006 Page 18

of HDCV or PCECV produce VNA titers >0.5 IU/mL by days 14-49 and provide superior long-term 

immunity compared to a two-dose series.

Several studies have been conducted on the safety of rabies biologics. For HDCV, mild and self-limited 

local reactions were reported in 60%-90% of vaccine recipients, including injection site pain, redness, 

swelling and induration. Mild and systemic reactions were reported in 7%-56% of vaccine recipients, 

including fever, headache, dizziness and gastrointestinal symptoms. Systemic hypersensitivity reactions 

were reported in 6% of vaccine recipients following booster doses. These reactions were believed to be 

associated with betapropriolactone-altered human albumin.

For PCECV, local reactions were reported in 11%-57% of vaccine recipients, including injection site pain, 

redness, swelling and induration. Mild and systemic reactions were reported in 0%-31% of vaccine 

recipients, including fever, headache, dizziness and gastrointestinal symptoms. Data collected from 

VAERS from 1997-2005 showed 30 adverse events/100,000 doses, two serious adverse events/100,000, 

0 vaccine-related deaths, and 0 vaccine failures. For HRIG, local and mild reactions are common. 

Systemic reactions are typically mild and self-limited. Four studies showed that no serious adverse 

events were reported when HRIG was co-administered with HDCV.

Rare, individual case reports of neurologic adverse events following rabies vaccination have been 

reported. Five cases of neurologic illness resembling Guillain-Barré syndrome (GBS) occurring after 

treatment with HDCV or PCECV were identified. One case of acute neurologic syndrome involving 

seizure activity was reported following the administration of HDCV and HRIG. Another case of acute 

CNS demyelination was reported following the administration of HDCV. In none of these cases has a 

causal association between rabies immunization and the adverse outcome been established

Dr. Martin Meltzer, of CDC, presented a study on the CE of rabies PEP. For the purposes of his study, 

CE was modeled as “net cost in dollars per life saved due to the administration of PEP.” The model 

included three CE ratios to demonstrate average, least and most CE. Several assumptions were made in 

the study. Death would be the only outcome of clinical cases of human rabies. PEP for rabies essentially 

would be 100% effective in preventing a clinical case of rabies when given as recommended. The study 

was conducted from a societal perspective over a one-year timeline. No costs were discounted with the 

exception of value of life lost. All costs were adjusted to 2004 dollars.

Cost data were extracted from public health reports published in 1998 and a study in press. Average, 

minimum and maximum costs of biologics ranged from $2,315-$4,831; hospital and physician charges 

ranged from $584-$1,423; and patient indirect costs ranged from $161-$2,161. To determine the dollar 

value of life, average present values of expected future lifetime earnings and housekeeping services 

assumed an average life span of 75 years and were discounted at 3%. Based on this formula, the value 

of human life weighted by age and gender was estimated at ~$1.1 million.

The probability of rabies transmission was difficult to estimate in the study due to the lack of data, except 

when animals were tested positive. To overcome this challenge, a panel of 10-12 experts used the 

Delphi technique to estimate potential exposure in seven different scenarios. The expert panel provided 

a broad range of probabilities of rabies transmission in the various scenarios. In addition to the baseline 

cost scenario, two sensitivity analyses were performed. In cost scenario 2, all PEP-associated costs were 

doubled and the baseline value of human life was maintained. In cost scenario 3, the value of human life 

was doubled and the cost of PEP was unchanged.

Cost-Effectiveness (CE) of Rabies PEP

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Key findings of the study are summarized as follows. Administration of PEP would result in cost savings if 

a skunk or rabies-positive animal bit an individual. Administration of PEP would result in a baseline cost 

of $2.9 million-$4 billion from possible bat bite exposure, dog bite or lick, cat bite or lick, or exposure to a 

rabid human. However, for each scenario depicting potential exposure to rabies, there was a wide range 

of CE ratios. For example, in the case of a possible bat bite exposure, the CE ratio ranged from net 

savings to a net cost of $8.4 billion. The sensitivity analyses, involving cost scenarios 2 and 3, also 

showed wide CE ratios that ranged from cost savings to $17 billion per life saved.

Overall, the study demonstrated cost savings if an individual was bitten by a rabies-positive rabid animal, 

skunk or another animal from the reservoir/vector species. On average, PEP was not found to be cost 

saving in the other rabies transmission scenarios. An extremely wide range of CE was observed in most 

of the scenarios. The study was limited due to three major factors. Efforts to place a dollar value on 

human life continue to be a source of debate. The probability of rabies transmission was the most 

important factor input into the model, but these estimates tremendously varied. Some scenarios of rabies 

transmission were not included in the model.

CDC conducted a peer review of the study. Two major comments by the reviewers focused on cost 

savings versus CE and the sensitivity analyses. The authors responded to the reviewers as follows. 

Cost savings do not automatically infer CE. No scientific threshold has been established to date to define 

CE. Similar to any other scheme, doubling of the values is arbitrary.

Dr. Manning summarized important components of the workgroup’s draft revised recommendations. No 

substantial changes were made to the recommended approach to rabies prophylaxis. Wording changes 

were made to clarify and specify the prophylaxis recommendations and explain difficult exposure 

scenarios. No new anti-rabies biologics have been developed for use in the United States since ACIP 

approved recommendations on human rabies prevention in 1999. No changes to the immunization 

schedule were recommended.

All tables and text would be updated to reflect that rabies vaccine adsorbed is no longer available for 

rabies prophylaxis. A systematic review of the available evidence was added to demonstrate the 

effectiveness and safety of rabies biologics. The number of references in the current draft statement 

increased from 118 to 215. New data on the economics of rabies PEP were added. New information on 

human rabies treatment considerations was included.

Dr. Manning’s summary of specific changes to the workgroup’s draft revised recommendations is outlined 

below.

Rabies PEP. The introduction will emphasize the following points. PEP administration is a medical 

urgency rather than a medical emergency. Appropriate management of potential human exposure 

requires an accurate risk assessment. Because rabies biologics are valuable resources and are 

periodically in short supply, benefits and harms should be balanced. Clinicians are strongly encouraged 

to consult with state or local pubic health officials in determining whether PEP would be needed. PEP 

recommendations depend on associated risks, including type of exposure, animal rabies epidemiology, 

circumstances of the exposure incident, and availability of exposing the animal for observation and rabies 

testing. Rabies prophylaxis is not risk-free.

The “types of exposure” section will contain several sub-sections. The two major categories will be “bite 

exposures” and “non-bite exposures.” The workgroup did not propose modifications to these basic 

Proposed Recommendations and ACIP Vote on Rabies PEP and Preexposure Prophylaxis

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definitions. The “non-exposures” sub-section will highlight situations that do not warrant PEP 

administration: (1) petting or handling of an animal, (2) contact with blood, urine or feces, (3) contact of 

saliva with intact skin, and (4) contact with non-mammals.

The “special considerations” sub-section will provide updated information on two types of exposures. 

First, bat exposures require a thorough evaluation. The risk of rabies from a bat encounter might be 

difficult to determine due to limited injury inflicted by a bat bite or inaccurate recall of a bat encounter. 

“Some bat-related rabies viruses may be more likely to result in infection after inoculation in superficial 

epidermal layers.” (Proposed new language) Any direct contact between a human and bat should be 

evaluated for exposure unless the individual is reasonably certain that a bite, scratch or mucous 

membrane exposure did not occur. Second, human-to-human transmission of rabies has occurred in 16 

cornea, solid organ and vascular tissue transplant recipients in the United States and four other countries. 

No laboratory-confirmed cases from human-to-human exposures have been observed other than the 

transplant cases.

The “wild terrestrial carnivores” sub-section will emphasize that all bites from raccoons, skunks and foxes 

should be considered as possible exposures. “PEP should be initiated as soon as possible following 

exposure to such wildlife unless (1) the animal is available for diagnosis and public health authorities are

facilitating expeditious laboratory testing or (2) it is already known that brain tissue from the animal has 

tested negative.” (Proposed new language) If PEP was initiated and animal tests were negative based 

on appropriate laboratory diagnostic testing, PEP should be discontinued.

Rabies Preexposure Prophylaxis. All preexposure tables and text would be updated to reflect the 

unavailability of intradermal administration of preexposure vaccination and rabies vaccine adsorbed for 

rabies prophylaxis. Preexposure vaccination should be offered to persons in high-risk groups. There are 

four risk categories based on the nature of the risk. No changes were proposed for the “continuous” risk 

category. Typical populations in the “frequent” risk category were expanded to include “all persons who 

frequently handle bats” regardless of location in the United States or throughout the world because of the 

existence of lyssaviruses on all continents except Antarctica. Typical populations in the “infrequent” risk 

category were revised as follows: “Veterinarians and terrestrial animal control workers in areas where 

rabies is uncommon to rare.” No changes were proposed for the “rare” risk category.

Contact information will be provided on indigent patient programs offered by sanofi pasteur and Novartis 

to ensure that uninsured or under-insured patients receive rabies biologics. Data will be highlighted on 

the treatment of human rabies patients. Rabies has the highest case fatality rate of any infectious 

disease. No proven effective treatment is recognized after onset of illness. Of six surviving cases, only 

one survived without rabies vaccination. Rabies vaccination after onset of illness is not recommended 

and might be detrimental. At a minimum, primary health considerations should focus on comfort care and 

adequate sedation of the patient in an appropriate medical facility after a definitive diagnosis is made. 

Aggressive and experimental therapies are currently under evaluation.

Precautions for safe clinical management of rabies patients will be outlined. Human rabies patients pose 

no greater risk to healthcare personnel than patients with more common bacterial and viral infections. 

Routine delivery of healthcare to a patient with rabies is not an indication for PEP unless the healthcare 

worker is reasonably certain that he or she was bitten by the patient or that his/her mucous membranes 

or nonintact skin was exposed to potentially infectious saliva or neural tissue. Medical staff should 

adhere to standard precautions as outlined by the Hospital Infection Control Practices Advisory 

Committee, particularly during incubation and suctioning. These precautions include gloves, gowns, 

masks, eye protection and face shields.

The critical components of human rabies prevention will be emphasized, such as enhanced public health 

education about rabies, domestic animal vaccination, responsible pet ownership, rapid and accurate 

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ACIP Meeting Minutes October 25-26, 2006 Page 21

laboratory testing, and modern stray animal control. The recommendations will note that timely and 

appropriate human prophylaxis will prevent human rabies, but is largely unnecessary if these other basic 

public health and veterinary programs are operative for functional zoonoses prevention and control. 

Several ACIP members and other participants made suggestions to strengthen the recommendations.

• The proposed language in the “infrequent” risk category for rabies preexposure 

prophylaxis should be changed as follows: “Veterinarians and terrestrial animal control 

workers in areas where rabies is uncommon to rare, including workers who work in areas 

where rabies is uncommon to rare.”

• CDC should frequently update its web site with guidance for front-line workers because 

ACIP’s recommendations on human rabies prevention are only revised every seven

years.

• New language should be included in the recommendations to clarify the use of rabies 

prophylaxis in HIV-positive persons and other IC populations. For example, the new text 

could specify that “additional doses should be administered to IC persons until an 

adequate serologic titre is achieved.”

• New language should be included in the recommendations to clarify the use of rabies 

prophylaxis for common and indirect non-bite exposures, particularly those that result in 

an extensive amount of time for evaluation.

• New language should be included in the recommendations to specify when rabies 

prophylaxis should be administered following a bat bite.

• The recommendations should be revised to provide specific guidance for persons who 

travel to or reside in areas where rabies is enzootic, such as Peace Corps workers and 

their children.

• Contact information for CDC and state health departments should be highlighted or 

featured in boxes in the recommendations. This approach would allow clinicians to easily 

and rapidly locate resources and obtain guidance on difficult scenarios.

Dr. Abramson entertained a motion to approve the proposed recommendations for rabies PEP and 

preexposure prophylaxis. A motion was properly placed on the floor and seconded by Mr. Beck and Dr. 

Hull, respectively.

ACIP passed the amended recommendation by a majority vote:

• 14 in favor: Abramson, Allos, Beck, Gilsdorf, Hull, Lett, Lieu, Morita, Morse, Neuzil, 

Stinchfield, Sumaya, Treanor, Womeodu.

• 1 abstention: Baker.

• 0 opposed.

Drs. Manning and Rupprecht explained that ACIP’s recommendations on rabies PEP and preexposure 

prophylaxis serve as a living document. As a result, they confirmed that suggestions made during the 

meeting to strengthen the recommendations would be considered. They also encouraged the members 

to submit additional comments for consideration and inclusion in the next iteration of the statement.

CHILD/ADOLESCENT IMMUNIZATION SCHEDULE (CAIS)

The series of presentations and ACIP’s discussion and vote on the CAIS are set forth below.

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Dr. Gregory Wallace, of CDC, highlighted key milestones that occurred from 1983-2006 in developing 

immunization schedules for children and adolescents. In 1983, ACIP published the first schedule for 

“normal infants and children” through 16 years of age. In 1995, an annual harmonized childhood 

immunization schedule was created and approved by ACIP, the American Academy of Pediatrics (AAP), 

and the American Academy of Family Physicians (AAFP). In 2003, a new format for the childhood 

immunization schedule was adopted with catch-up bars and a pre-adolescent assessment. In 2003, the 

name of the “childhood immunization schedule” was changed to “CAIS” with the addition of a stand-alone 

catch-up schedule. For the 2007 CAIS, a proposal was made to split the schedule into two, i.e., for 

children and adolescents and elimination of the red box for selected populations.

The Childhood/Adolescent Immunization Workgroup presented preliminary findings and initial focus group 

results on the CAIS during the June 2006 meeting. Since that time, the workgroup has been addressing 

ACIP’s comments on the CAIS. The workgroup is currently exploring the potential to harmonize formats 

between the CAIS and adult schedules; revisiting the possibility of providing a routine-only schedule; 

identifying strategies to utilize the catch-up schedule more prominently; and developing a separate highrisk schedule. During the current meeting, the workgroup would make a series of presentations and 

present its proposed recommendations to facilitate ACIP’s discussion and vote on the 2007 CAIS.

Ms. Sarah Clark, of the University of Michigan, announced that focus groups were held with 69 

immunization providers following the June 2006 ACIP meeting to obtain input on the proposed twoschedule format and three potential schedules: (1) 0-6 years of age on page 1 and 7-18 years of age on 

page 2; (2) 0-10 years of age on page 1 and 11-18 years of age on page 2; and (3) 0-6 years of age on 

page 1 and 11-18 years of age on page 2. Feedback was also gathered from the providers on individual 

features within the proposed formats and potential formats for the catch-up schedule.

The 69 immunization providers who participated in the focus groups were resident and attending 

pediatricians and family physicians, nurse practitioners, physician assistants, registered nurses, and 

licensed practice nurses. The providers represented local health department immunization clinics, urban 

federally qualified health centers, suburban and rural primary care clinics, and urban pediatric clinics.

Consensus on the format of two schedules was not reached across provider group, setting or type. The 

preference for the 0-6/7-18 year format was driven by the preference for the 0-6 schedule. None of the 

providers were in favor of excluding the 7-10 age group. Providers who supported the 0-6/7-18 year 

format made the following comments. “The 0-6 page is clean and easier to read.” “The format is 

consistent with the concept that one phase of immunization reaches children through kindergarten shots, 

while the next phase reaches older children.” “The format matches the recommendations most closely 

because some vaccines are not given after this age range.”

Providers who supported the 0-10/11-18 year format made the following comments. “The inclusion of all 

information on one schedule would be the next best thing.” “This format would provide more information 

because my institution’s web site would only post one page.” All providers were in favor of the yellow 

boxes for primary recommendations in the 11-12 year age group. Nearly all providers disliked the green 

and purple bars because the format was viewed as overwhelming and redundant with the catch-up 

schedule. The majority of providers initially supported the one-table version for the catch-up schedule. 

Overview

Results of the Immunization Schedule Focus Groups

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ACIP Meeting Minutes October 25-26, 2006 Page 23

However, most providers eventually preferred the two-table format because agreement could not be 

reached on an appropriate format for DTaP/Tdap.

The providers made overarching comments for ACIP to consider in formulating its recommendations on 

the immunization schedules. Recommendations for high-risk populations are typically confusing and do 

not contain sufficient details. The ranges of recommended ages can be problematic. The intervals 

between doses with exceptions are unclear. “Catch-up” is not clearly defined as actual catch-up, a 

recommendation, option or unnecessary action. Overall, the providers generally preferred two schedules 

rather than one schedule for the 0-18 year age group. Providers who favored two schedules preferred 

the 0-6/7-18 year format. Providers preferred two tables for the catch-up schedule rather than one table 

due to complexities associated with DTaP/Tdap.

Dr. Angela Calugar, of CDC, reported that several factors were considered when changing the 

immunization schedule, such as its growing complexity, the need for a better and more user-friendly 

format, and approval of the new vaccines in 2006. A two-phase qualitative research project was 

conducted with immunization providers. Preliminary findings from this activity and initial drafts of the 

schedule were presented to ACIP during the June 2006 meeting. Collaborative efforts were undertaken 

with subject matter experts (SMEs) to refine the content of footnotes. Final drafts of the immunization 

schedule would be presented to ACIP during the current meeting for review and formal approval.

The current immunization schedule for the year 2006 targets ages from birth through 18 years and 

includes 14 combined or single-dose antigen vaccines. The current catch-up schedule is split into two 

tables for children 4 months through 6 years of age and 7-18 years of age.

Immunization providers in the focus groups were most frequently concerned about (1) overcrowding of 

the immunization chart; (2) the purple bar for the assessment of children 11-12 years of age; (3) 

confusion in the red box for special populations; and (4) insufficient or an overabundance of details in the 

footnotes. 

The workgroup revised the schedule for consistency with several recent ACIP recommendations, i.e., 

approved rotavirus and HPV vaccines in February and June 2006, respectively. Influenza vaccine 

recommendations were expanded to include children 24-59 months of age and the second dose of 

varicella vaccine was approved. 

The current immunization schedule was split to reflect the 0-6 and 7-18 year age groups. The purple bar 

for the adolescent visit and the red-dotted box for special populations were removed from the schedule. 

Other major changes were made to the presentation of the fourth dose of the hepatitis B (HepB) vaccine, 

footnotes for the Haemophilus influenzae B (Hib) vaccine, and the overall order of the vaccines. These 

changes were made in response to the focus group findings and some programmatic considerations. 

The workgroup performed a thorough analysis when suggestions by the immunization providers widely 

varied or were contradictory.

The workgroup’s next steps will be to address outstanding issues and concerns raised by immunization 

providers who participated in the focus groups:

• Lack of details for high-risk groups.

• Dislike of the colored bars in the 7-18 year age group schedule.

• Confusion in the recommended age ranges and intervals between doses with exceptions.

Update on the 2007 Immunization Schedule for Ages 0-18 Years

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ACIP Meeting Minutes October 25-26, 2006 Page 24

• Unclear presentation of the MCV4 for the 15-year-old dose.

• Unclear definitions and indications for using catch-up bars and schedules.

• No harmonization between the CAIS and adult schedule.

• The possibility of developing a special schedule for high-risk children and removing 

catch-up bars from routine schedules.

Dr. Calugar presented the following proposed drafts to facilitate ACIP’s discussion and vote: (1) 

immunization schedules for the 0-6 and 7-18 year age groups, (2) the catch-up schedule, and (3) footnote 

formats for all three schedules.

ACIP commended the workgroup on making tremendous improvements to enhance the immunization 

schedules. The members found the proposed drafts to be clearer and easier to read. Several members 

and other participants made suggestions for the workgroup to consider in further refining the documents.

• The title should be changed to “11-12 years” on the schedule for the 7-18 year age 

group. The word “assessment” should be deleted to be consistent with the other titles.

• Dr. Amy Middleman, the liaison member for the Society for Adolescent Medicine, should 

be engaged in future efforts to revise the schedules. Dr. Middleman’s expertise could 

assist the workgroup in creating a separate schedule for adolescents. This change would 

be consistent with current efforts to shift toward specific preventive care strategies for this 

age group. Moreover, ACIP should consider whether a new adolescent workgroup 

should be formed.

• The web-based version of the schedule should be revised to include hyperlinks to ACIP’s 

recommendations for each vaccine. A separate web page should also be developed 

specifically for IC persons.

• A uniform abbreviation for rotavirus should be created because both “Rota” and “RV” are 

used in the field.

• The green and purple bars in the schedule for the 7-18 year age group should be 

extended to ages 7-10 years for both high-risk and catch-up.

• Focus groups should be conducted with obstetricians, gynecologists and adult physicians 

because these providers are not typical users of the schedules. Input from these 

practitioners on the schedule for the 7-18 year age group would be particularly helpful 

because older adolescents present to these providers rather than pediatricians.

• The contradiction in footnote 10 in the schedule for the 7-18 year age group should be 

resolved. Most notably, guidance to “administer varicella vaccine at least three months 

apart” and “not repeat the second dose if administered >28 days following the first dose” 

is inconsistent. The contradiction could be resolved with the following revision: “A threemonth interval is recommended. If >28 days have passed, however, repeating the dose 

is unnecessary.”

Dr. Abramson entertained a motion to approve the proposed draft immunization schedules with the 

condition that the workgroup would address ACIP’s comments. A motion was properly placed on the floor 

and seconded by Dr. Hull and Ms. Stinchfield, respectively. The motion was unanimously approved 

by all 15 voting members: Abramson, Allos, Baker, Beck, Gilsdorf, Hull, Lett, Lieu, Morita, Morse, 

Neuzil, Stinchfield, Sumaya, Treanor, Womeodu.

Drs. Pickering and Wallace confirmed that CDC would take several actions to address ACIP’s comments 

on the immunization schedules. One, CDC will revise the next version of the web-based interactive child 

ACIP Vote on the 2007 Immunization Schedule for Ages 0-18 Years

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ACIP Meeting Minutes October 25-26, 2006 Page 25

immunization schedule to allow users to type the child’s date of birth, enter the immunization history, and 

obtain output data on specific vaccines the child would need by a certain date. CDC will continue its 

internal discussions on potential strategies that could be applied to completely eliminate paper-based 

immunization schedules in the future.

Two, CDC will consult with its Education Branch and rotavirus SMEs to resolve the discrepancy between 

the “Rota” and “RV” abbreviations for rotavirus. Three, CDC will initiate discussions with the ACIP 

Varicella Workgroup and varicella SMES on potential wording changes that could be made to resolve the 

inconsistency in footnote 10 on the schedule for the 7-18 year age group.

INFLUENZA VACCINE

The series of presentations, ACIP discussions and public comments on the influenza vaccine are set forth 

below.

Dr. Joseph Bresee, Chief, Epidemiology and Prevention Branch, Influenza Divisiion, CDC, summarized 

surveillance data for the 2006-2007 influenza season. Laboratories participating in the WHO National 

Respiratory and Enteric Virus Surveillance System showed that 1% of samples submitted were positive 

with a fairly even split between influenza B and H1A viruses. H1 strains detected in the late spring/early 

summer and into the fall were closely related to vaccine strains. Data collected from sentinel provider 

networks on pneumonia and influenza (P&I) mortality in 122 U.S. cities showed that 1.3% of all visits to 

sentinel providers were attributable to influenza-like illness (ILI) less than the seasonal baseline. The P&I 

systems also showed a P&I mortality below epidemic thresholds.

To date, 40 states reported no influenza activity, six states reported sporadic activity, and two states 

reported local activity. The CDC laboratory will periodically perform adamantane- and neuraminidaseresistance testing on isolates during the influenza season. CDC does not expect the test results to 

change influenza recommendations for the 2006-2007 season.

Dr. Ban Allos, the Influenza Workgroup Chair, reported that both ACIP and AAP currently recommend two 

doses of influenza vaccine for children <9 years of age in the first year they receive vaccine. During the 

June 2006 meeting, ACIP voted not to change the recommendation for children <9 years of age who 

received only one initial dose of vaccine. ACIP took this action due to the lack of evidence to support a 

change in the recommendation.

In October 2006, however, the AAP Committee on Infectious Diseases adopted a different 

recommendation stating that children <9 years of age should receive two doses of vaccine the following 

year. The workgroup will collaborate with AAP to develop communication messages or frequently asked 

questions to address differences between the two sets of recommendations. CDC expects to create the 

list of questions and answers over the next two to three weeks.

During the June 2006 ACIP meeting, the workgroup also proposed a potential time frame to modify 

annual influenza vaccination recommendations. Critical issues would be assessed and addressed in 

2006-2008. The possibility of expanding the recommendations to include all school-aged children 5-18 

years in 2008-2009 would be explored. The recommendations could potentially be expanded to include 

household contacts and caregivers of school-aged children in 2010-2011. Universal vaccination would be 

Overview

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ACIP Meeting Minutes October 25-26, 2006 Page 26

recommended if necessary and the recommendations would be extended to persons 18-49 years of age 

in 2012-2013.

Several ACIP members expressed concerns that the proposed time frame was too long, particularly after 

the inclusion of household contacts of school-aged children. The members also requested clarification on 

data that would be used to inform ACIP decision-making and whether these data would be readily 

available. However, feedback from ACIP members to the workgroup to address these concerns was 

limited following the June 2006 meeting.

The workgroup identified several critical factors that need to be assessed and addressed before the 

influenza vaccination recommendations are changed. New or existing surveillance systems should be 

developed or enhanced to assess influenza illness. Vaccine safety and effectiveness should be 

monitored. Capacity to annually vaccinate school-aged children and working adults should be evaluated. 

Availability of an adequate vaccine supply should be assured.

In its next steps, the workgroup will meet to discuss vaccine safety and effectiveness, adequacy of 

supply, and feasibility of expanding the recommendations to include school-aged children. The 

workgroup will be mindful of the importance of improving vaccine delivery to existing target groups during 

these efforts. Data collected from 1989-2004 showed that the most progress in influenza vaccination was 

among persons >65 years of age, while the least progress was among healthcare workers. The 

workgroup acknowledged that public awareness and education of providers and practices must be 

strengthened to improve influenza vaccination of existing target groups.

Several ACIP members made suggestions for the workgroup to consider in future efforts to expand the 

influenza vaccination recommendations.

• The recommendations should be strengthened with the following language to advance 

toward universal vaccination: “Influenza vaccine would be appropriate for individuals with 

an interest in decreasing their risk for acquiring influenza in the current season.”

• The proposed time frame to expand the recommendations to universal vaccination 

should be expedited for consistency with the availability of vaccine for pandemic 

influenza. This goal could be achieved by changing the two-year increments to one-year 

increments in the proposed time frame. However, the expedited time frame should 

ensure that the supply can meet the demand.

• Stronger efforts should be made to educate the public on the risks and benefits of 

influenza vaccination during pregnancy.

• The clinical realities of ordering vaccine should be considered when ACIP’s influenza 

recommendations are developed, expanded or revised. For example, some pediatricians 

expressed concern that the expanded recommendation to include children 24-59 months 

of age occurred after pre-booking. As a result, the amount of vaccine was not sufficient 

to meet the expectations and needs of the expanded population.

• ACIP should be given an opportunity to re-review cost effectiveness data on influenza 

vaccination during the workgroup’s ongoing efforts to expand the recommendations.

• The list of questions and answers that will be developed should contain accurate 

guidance on the appropriate time to administer influenza vaccine. For example, the 

public has an incorrect perception that influenza vaccine must be administered in 

September and should not be given after November. 

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Dr. Wallace reported that 25 million influenza doses were distributed by the end of September 2006 and 

~50 million doses were available as of October 20, 2006. By October 31, 2006, up to 75 million doses 

are projected to be available. More doses were distributed from October 13-20, 2006 compared to the 

previous week. The peak distribution by month in the current season is projected to be the same as last 

year, but later than an early season, such as 2002. The actual peak is anticipated to be larger and occur 

later than any previous season.

The possibility exists of increasing the supply to 110-115 million doses due the recent approval of the 

GlaxoSmithKline FluLavalTM vaccine. The vaccine could be distributed if the demand is sustained. 

Overall, manufacturers are making efforts to address concerns about vaccine delays, specific vaccine 

recipients, and the 0.25 thimerosal-free vaccine for young infants.

sanofi pasteur. Dr. Philip Hosbach reported that sanofi pasteur publicly announced delays in influenza 

vaccine by ~3 weeks. Of the 59% of vaccine sanofi pasteur will distribute by October 27, 2006, 46% will 

be to the public sector. Of all targeted doses, 85% will be distributed to private physicians, public health 

providers and hospitals. By the first week in November 2006, sanofi pasteur will distribute all doses of the 

0.25-mL preservative-free influenza vaccine to pediatricians for children <3 years of age. To date, 

>100,000 doses of this vaccine have not been ordered.

A new enclosed facility is under construction that will double sanofi pasteur’s capacity in 2008-2009 and 

allow for production of 100 million doses of influenza vaccine. In 2007 or 2008, sanofi pasteur expects to 

build a new fill and formulation facility that would allow for an expansion over the current 8-9 million doses 

of preservative-free vaccine. sanofi pasteur initiated cell culture clinical trials and was awarded six 

requests for proposals. The new research projects include the stockpile, H5N1 vaccine, and pandemic 

influenza capability and capacity in clinical trial vaccine production. sanofi pasteur is also exploring the 

possibility of immunizing children <6 months of age in clinical trials. sanofi pasteur is producing new 

formulations and methods to deliver influenza vaccine that would assist in improving immune response in 

elderly persons and other populations.

Protein Sciences Corporation (PSC). Dr. Manon Cox reported that PSC is developing a recombinant 

hemagglutinin-based vaccine made in cell culture. The vaccine is 90%-95% pure, contains three times 

more active ingredients than the currently licensed vaccine, and does not contain any preservatives or 

adjuvants. The vaccine can be used in egg-allergic persons.

PSC has conducted >10 clinical trials on the vaccine to date and published these data in peer-reviewed 

journals. A field study showed 100% protection of the vaccine against cell culture-confirmed influenza in 

persons presenting with CDC-ILI.. Solid immunogenicity in elderly persons was observed as well. PSC 

has been placed on FDA’s accelerated approval pass and expects to begin filing its biologic license 

application (BLA) of the vaccine in the first half of 2007. Depending on when FDA approves PSC’s BLA, 

5-10 million doses of the vaccine could be available for the 2007-2008 influenza season.

Novartis Pharmaceuticals. Dr. Theodore Tsai reported that the 25 million doses Novartis will have 

shipped by the end of October represent ~60% of the total production for the year. Novartis expects to 

ship ~40 million doses in the next influenza season and is making investments to increase the number of 

preservative-free doses in the near future.

Update on Cumulative Monthly Influenza Vaccine Distribution

Manufacturer Reports on the Future of Influenza Vaccine

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ACIP Meeting Minutes October 25-26, 2006 Page 28

Novartis recently completed Phase III trials on a Madin-Darby canine kidney cell-derived vaccine that is 

not produced with formaldehyde and contains no antibiotics, thimerosal or preservatives. Novartis is in 

the process of submitting a BLA for the cell culture influenza vaccine and recently broke ground on a new 

manufacturing facility in North Carolina that will be dedicated to the production of the vaccine in the 

United States. Overall, Novartis’ position is that the vaccine could have advantages in manufacturing 

flexibility; might provide an opportunity to include more antigenically representative strains in the seasonal 

vaccine; and will offer an option for egg-allergic persons.

Novartis is the only distributor of an adjuvant influenza vaccine. Fluad was first licensed in Europe in 

1997 and is currently licensed in >20 European countries. To date, 25 million Fluad doses have been 

distributed. Novartis is now exploring options to introduce an adjuvant vaccine in the United States in the 

future.

MedImmune, Inc. Mr. Mark Twyman reported that MedImmune acknowledges the merit in encouraging 

Americans to be immunized early in the season. This approach would facilitate several outcomes: 

stronger capacity to leverage available vaccine in the July-September time frame; benefits from 

completing the immunization series prior to the circulation of disease in communities; and greater 

opportunities for providers to administer two influenza vaccine doses to children.

MedImmune began shipping FluMist® doses to physicians in July 2006 for the current influenza season. 

All ~3 million doses were available for distribution prior to the end of September 2006. The remaining 

doses are now available for immediate shipment to physicians. MedImmune has a bulk capacity of 90 

million FluMist® doses and will have capacity next year to fill and finish ~7 million doses for market 

distribution.

MedImmune will increase its production capacity to 20 million doses for the 2008-2009 season and 35 

million doses thereafter. Depending on demand, MedImmune has the ability to invest additional capital to 

increase its fill and finish capacity to meet the bulk capacity of 90 million doses. MedImmune is currently 

focusing on the pediatric segment with respect to future product label changes, but has not yet 

determined a specific scope and timeline for other enhancements of the FluMist® label.

MedImmune assessed the potential demand curve if the current influenza vaccination recommendations 

were expanded to include age groups up to 18 years. The assessment showed that MedImmune could 

meet most of the vaccine requirement in 2008 to support the expanded recommendations and all of the 

vaccine requirement in 2009. Vaccine supply issues might not continue to serve as an impediment in the 

future due to the capacity of MedImmune and other manufacturers to meet demand if the influenza 

recommendations are expanded to include age groups up to 18 years.

Pending FDA approval of its supplemental BLA (sBLA), MedImmune would make FluMist available to the 

Vaccines for Children (VFC) eligible population under a contract with CDC. The VFC price would be 

discounted from the currently contemplated price of $18/dose for the next generation vaccine. As with 

FluMist®, MedImmune’s cold-adapted influenza vaccine (CAIV-T) will also be 100% free from thimerosal 

and preservatives pending FDA licensure.

GlaxoSmithKline (GSK). Dr. Margaret Rennels reported that GSK has made a significant commitment to 

expand global influenza vaccine production, introduce influenza vaccine to the United States, and 

develop new vaccine approaches. GSK has made a $2 billion investment to double manufacturing 

capacity of the FLUARIX platform in Dresden, German for a total of 60-70 doses per year. GSK’s 

purchase of ID Biomedical in Canada and expansion of this facility will result in production of ~75 million 

doses annually. GSK also procured the former Wyeth Manufacturing platform in Marietta and will convert 

and update this facility to produce the cell culture-based influenza vaccine.

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Licensure of the FluLavalTM vaccine in the United States will increase the total number of doses GSK can 

bring into the country to ~25 million doses this year. GSK will launch pediatric studies in the fall and will 

also introduce a preservative-free vaccine as soon as feasible. The initial pediatric studies will be

conducted with FLUARIX that contains trace thimerosal.

GSK has several novel vaccine approaches in early development. HHS awarded a contract to GSK to 

produce cell culture-based vaccines. GSK has been developing adjuvants for influenza vaccine since 

1989 under several ongoing programs, including adjuvant H5 vaccine, adjuvant trivalent inactivated 

vaccine (TIV) to improve the immune response in elderly persons, and adjuvant intranasal inactivated TIV 

vaccine.

CSL Biotherapies. Dr. Pickering read a statement that was submitted into the record by CSL 

Biotherapies. CSL completed the enrollment of 1,300 subjects for a clinical trial of its influenza virus 

vaccine. The randomized double-blind controlled trial was designed to evaluate safety and 

immunogenicity of the vaccine in healthy adults and is intended to support accelerated approval for the 

2007-2008 season. CSL and the FDA Center for Biologics Evaluation and Research outlined a program 

to facilitate the submission of a BLA for a thimerosal-free single-dose pre-filled syringe and a multi-dose 

vial containing thimerosal as a preservative only.

CSL-branded influenza virus vaccines are already approved and marketed in 16 countries worldwide. 

CSL’s thimerosal-free single-dose syringe is approved in Europe for persons >6 months of age. CSL also 

provides bulk influenza vaccine for sale in 24 countries. CSL is expanding its manufacturing facilities to 

be able to supply ~20 million doses to the United States by 2010. Pending FDA licensure, CSL’s 

influenza virus vaccine would be marketed by its U.S. commercial vaccine entity.

Baxter Healthcare Corporation. Dr. Peter Khoury reported that Baxter produces its viral cell-derived 

influenza vaccine in a commercial-scale and good manufacturing practices (GMP) approved facility in 

Czech Republic. Baxter has two ongoing developmental programs. The seasonal vaccine is a split viral 

trivalent vaccine that is free from antibiotics and preservatives, independent of egg supply, and packaged 

as pre-filled syringes. The process to produce the vaccine is ~12 weeks from strain availability to actual 

availability of the pre-filled syringes.

Baxter intends to formulate the seasonal vaccine for both adult and pediatric use and expects to file an 

investigational new drug application in the United States over the next two weeks. Baxter will initiate 

clinical trials of the seasonal vaccine in the first quarter of 2007 with an adult population and in the third 

quarter of 2007 with a pediatric population. Baxter expects to obtain approval for the adult indication 

during the second quarter of 2009 and the pediatric indication during the second quarter of 2011.

Baxter developed its pandemic whole virus viral cell vaccine with the Vietnam 1203 strain of H5N1. 

Baxter recently completed Phase I/II clinical trials of the vaccine in Austria and Singapore. The study 

showed that the vaccine was safe and had an excellent tolerability profile. No dose response or adjuvant 

effects were observed. Baxter will initiate clinical trials of the pandemic vaccine in the second half of 

2007 with an adult population and in second half of 2008 with a pediatric population.

Dr. Robert Walker, of MedImmune, presented data to demonstrate the safety and efficacy of CAIV-T in 

young children. FluMist® is currently indicated for active immunization for the prevention of disease 

caused by influenza A and B in healthy persons 5-49 years of age. FluMist® is a trivalent live attenuated 

CAIV-T Safety and Efficacy Data

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influenza vaccine that is stored frozen, thimerosal-free, needle-free and administered as a nasal mist. 

The dose volume of 0.5 mL (0.25 mL per nostril) is administered as a single annual dose in persons 9-49 

years of age. However, persons 5-9 years of age with no previous FluMist® vaccination would receive 

two doses.

Several manufacturing and other developments have occurred since FluMist® was approved in June 

2003. A new bulk manufacturing facility in the United Kingdom was approved in December 2005. The 

new facility provides MedImmune with capacity to manufacture up to 90 million trivalent bulk doses. The 

plasmid rescue technique for FluMist® manufacturing was approved in June 2006. MedImmune has 

made this reverse genetics technology available to other influenza vaccine manufacturers. MedImmune 

received approval from FDA to release the first doses of FluMist” in July 2006 and the remaining available 

doses by the end of September 2006. MedImmune will continue its efforts to make FluMist® available as 

early as possible in the season.

Both the frozen FluMist® formulation and the new CAIV-T formulation are preservative-free and contain 

sucrose phosphate glutamate (SPG) as excipients. However, several characteristics distinguish the two 

vaccines. FluMist® is licensed in the United States, while CAIV-T is an investigational vaccine. CAIV-T 

is refrigerator stable, while FluMist® requires storage in the freezer. CAIV-T contains other excipients in 

addition to SPG, such as arginine and hydrolyzed porcine gelatin. The dose volume of CAIV-T is 0.2 mL 

(0.1 mL per nostril).

MedImmune filed an sBLA for CAIV-T in September 2005 to provide FDA with Phase III trial data. The 

study was designed to bridge CAIV-T and FluMist®, demonstrate analytic comparability between the two 

formulations, and evaluate immunologic and clinical equivalents of the vaccines. MedImmune filed a 

second sBLA in July 2006 to expand the CAIV-T label to include children 12-59 months of age with no 

history of asthma or wheezing. This indication was derived from a series of risk/benefit analyses of the 

comparative study. FDA is currently reviewing the Phase III trial data and has scheduled the Prescription 

Drug User Fee Act review for May 2007.

A substantial body of data showed that FluMist® and CAIV-T had high efficacy in young children. 

Cohorts in placebo controlled trials ranged from ~1,600-3,000 children. The efficacy of FluMist® or CAIVT ranged from 73%-93% and was statistically significant. Both cohorts in two large TIV-controlled studies 

had ~2,000 children. The studies compared CAIV-T and TIV and showed statistically significant results. 

CAIV-T would have additional efficacy of 53% and 35%, respectively, compared to TIV. Both studies 

were recently published.

The CP111 pivotal study was designed as a multinational randomized and double-blind study that used 

TIV manufactured by sanofi pasteur as an active control. The cohort was 8,475 children 6-59 months of 

age, including those with underlying medical disorders. However, immunocompromised children and 

those with severe asthma and recent wheezing within six weeks were excluded from the study. The 

primary efficacy endpoint was culture-confirmed modified CDC-ILI that required the presence of a fever 

plus at least one other symptom on the same or consecutive days, such as cough, sore throat, runny 

nose or nasal congestion.

During the CP111 study, the first immunizations were completed in advance of the onset of the 

immunization season. Significantly fewer cases of influenza were seen during the onset of the season in 

the CAIV-T group compared to the TIV group. Differences in influenza attack rates became more 

pronounced as the season progressed. The relative efficacy of CAIV-T of 54.9% was statistically 

significant for culture-confirmed modified CDC-ILI caused by any wild-type strain. The relative efficacy of 

CAIV-T was also statistically significant for culture-confirmed modified CDC-ILI caused by specific strains: 

89.2% for H1N1 and H3N2 for 79.2%. However, the strain-specific relative efficacy of CAIV-T for the B 

strain of 16.1% was not statistically significant.

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Rates of serious adverse events were similar in the CAIV-T and TIV treatment groups. CAIV-T was 

associated with increases in runny or stuffy noses, while TIV was associated with increases in injection 

site reactions. Children were followed during the study period for medically significant wheezing (MSW) 

based on a prospective case definition. For purposes of the CP111 study, “MSW” was defined as 

wheezing documented by a healthcare provider and associated with an intervention.

In children >2 years of age, no significant differences in MSW rates were seen between the CAIV-T and 

TIV treatment groups. In children <2 years of age in the two-dose group, a statistically significant 

increase of MSW was seen within the pre-specified safety evaluation period of 42 days after dose 1. 

CAIV-T was associated with a 3.2% increase in MSW in 55 children, while TIV was associated with a 2% 

increase in MSW in 34 children. Increases in MSW cases were not observed in the first week following 

vaccination. MSW rates were not statistically different beyond 42 days post-vaccination through the end 

of the study period or after dose 2.

The CP111 study did not show differences in the severity of MSW between the CAIV-T and TIV treatment 

groups among children <24 months. Rates were also comparable between the two groups in terms of 

hospitalization for MSW and the median duration of hospitalization. MSW was not associated with any 

deaths, admission to intensive care units or use of ventilators. Recurrent MSW rates were 3.2% in the 

CAIV-T group and 2.8% in TIV group with >1 recurrence and 2.6% in the CAIV-T group and 4% in the TIV 

group with >2 MSW recurrences.

Post-hoc exploratory analyses were performed for the entire study period to assess MSW, 

hospitalizations due to any cause, and a potential association from prior history of wheezing or asthma. 

CAIV-T was associated with an increase in all-cause hospitalization in children 6-11 months of age. 

CAIV-T was associated with higher hospitalization rates in children 12-47 months of age with a history of 

wheezing, but these rates were not statistically significant. CAIV-T was not associated with a risk of 

hospitalization in children 12-59 months of age without a history of wheezing. CAIV-T was associated 

with higher MSW rates in children 12-47 months of age with a history of wheezing. Overall, the post-hoc 

exploratory analyses demonstrated that CAIV-T had significant benefits in terms of reducing influenza in 

all age groups of children with and without a history of wheezing.

The CP123 study was conducted in 2005 with the same vaccine formulations as the CP111 study to 

analyze immunogenicity. The CP123 cohort was 52 children 6-35 months of age. The children received 

two doses of either CAIV-T or TIV. Serum hemagglutination-inhibiting antibody responses were 

assessed following both doses. Seroconversion rates were substantially higher following both CAIV-T 

doses and some of these rates were statistically significant.

Overall, CAIV-T was associated with superior efficacy against both matched and mismatched influenza. 

Based on data from the post-hoc exploratory analyses, MedImmune will not recommend the use of CAIVT in children <12 months of age until additional studies are conducted to better understand the increase in 

all-cause hospitalization in this population. MedImmune is currently seeking FDA approval of its 

proposed indication for use of CAIV-T in children 12-59 months of age.

CAIV-T might be associated with a higher rate of all-cause hospitalization in children up to 47 months of 

age with a history wheezing. CAIV-T appears to have a highly favorable risk/benefit profile in children 12-

59 months without a history of wheezing. Children with no history of wheezing accounted for 80% of all 

children 12-59 months of age in the CP111 study. An ongoing study demonstrated that the duration of 

protection of CAIV-T extended beyond 10-12 months in one season. MedImmune has submitted the 

CP111 data for publication.

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Dr. Neuzil pointed out that other published data with a large cohort of children showed different 

immunogenicity results with the H1N1 strain than the CP11 study. Dr. Abramson asked CDC to develop 

and distribute a table to ACIP by the February 2006 meeting. The table should list all licensed influenza 

vaccines, the current production status of each vaccine based on the manufacturer reports, and potential 

outcomes with vaccine production that might occur in the future.

Mr. Scott Laster is a parent of a child with autism who is showing phenomenal results from treatment. 

He pointed out that the manufacturer reports presented during the meeting and several published studies 

provide ACIP with sufficient information to recommend thimerosal-free vaccine for all doses in the next 

influenza season. For example, a 1999 study with children who received either thimerosal-free or 

thimerosal-containing vaccines showed that children with thimerosal exposure were 11 times more likely 

to develop autism than children with no exposure.

A 2004 study demonstrated that thimerosal interrupts or inhibits the methylation process. This process 

plays a key role in building neural pathways in the brain. A 2005 study with infant primates showed that 

thimerosal crosses the blood brain barrier and contains twice as much inorganic mercury compared to 

methyl mercury after entering the brain. Mr. Laster urged ACIP to recommend the removal of thimerosal 

from vaccines. He also asked ACIP to reiterate to the public that children and pregnant women should 

receive thimerosal-free vaccines. 

Ms. Allison Davis is a parent of autistic children. She received four thimerosal-containing vaccines in 

utero. She urged ACIP not to recommend mercury-containing vaccines for pregnant women because 

mercury is the second most neurotoxin on the planet. Ms. Davis reminded ACIP that its guidance and 

recommendations affect the lives of individuals throughout their entire lives.

Mr. Glenn Moise, of Families Fighting Flu (FFF), is a parent of a child who was nine months of age at the 

time of his death. His son died from complications due to influenza A prior to receiving his second 

influenza shot. Mr. Moise emphasized that FFF is a strong national and local advocate for influenza 

immunization for all children. He thanked ACIP for its continued efforts and focus on universal pediatric 

immunization.

Ms. Denise Palmer, of FFF, is a parent of a child who was 15 months of age at the time of her death 

from influenza A. She thanked ACIP for its ongoing efforts to expand the influenza recommendations.

 

Dr. Kristin Nichol, Chair of the Minnesota Coalition for Adult Immunization, announced that the American 

Lung Association (ALA) recently launched the national and regional “Faces of Influenza” initiative. The 

campaign involves the development of educational materials; distribution of public service 

announcements; creation of a web site; and publication of a portrait gallery book with photographs and 

personal stories of Americans who are in one of the high-priority groups recommended by ACIP for 

annual influenza vaccination.

The Faces of Influenza initiative was designed to demonstrate the seriousness of influenza as a potential 

deadly disease and emphasize the importance of prevention through vaccination. ALA will soon initiate 

several regional events to support the campaign. Dr. Nichol encouraged the public to view the portrait 

gallery book and other program materials at www.facesofinfluenza.org. 

Ms. Wendy Fournier, of the National Autism Association, is a parent of an autistic child who is six years 

of age. Her daughter received the HepB vaccine shortly after her birth and 212.5 μg of thimerosal from 

Public Comment Period

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ACIP Meeting Minutes October 25-26, 2006 Page 33

other vaccines over the next 15 months. Her daughter was diagnosed with autism at 18 months of age, 

but was later discovered to have heavy metal toxicity, food sensitivities, gut pain and encephalitis due to 

IgG and IgM auto antibodies to her brain consistent with vaccine injury.

Ms. Fournier described several milestones that have resulted in poisoning and destroying the immune 

system of her daughter and an entire generation of children. Merck had knowledge of the danger of 

mercury in its vaccines, but took no actions to protect the public. A manufacturer informed CDC in 1999 

of its capacity to provide a sufficient supply of thimerosal-free vaccine to meet the demand through the 

first half of 2000, but CDC did not order the thimerosal-free vaccine.

The bulk of thimerosal was removed from pediatric vaccines, but CDC added multiple influenza shots to 

the child immunization schedule and is still recommending influenza immunization for pregnant women. 

CDC continues to insist that mercury-containing vaccines are safe. ACIP has refused to state a 

preference for thimerosal-free vaccines. Studies have not been conducted to demonstrate that vaccines 

administered to children in a short period of time in accordance with the child immunization schedule are 

safe. Data have not been presented on the toxic components used in the production of vaccines.

Ms. Fournier urged CDC to reevaluate its vaccine program because the success of the program should 

be based on the protection of children’s health rather than uptake. She also urged ACIP to restore public 

confidence by creating a safer child immunization schedule and recommending that children and 

pregnant women receive thimerosal-free vaccines only.

Ms. Lyn Redwood, of Sensible Action for Ending Mercury-Induced Neurological Disorders (SafeMinds), 

noted that ACIP did not fully respond to the request she made during the June 2006 meeting. Although 

several vaccine manufacturers reported on future plans to produce preservative-free vaccines, ACIP still 

did not state its preference for thimerosal-free vaccines for infants, children and pregnant women during 

the current meeting.

Ms. Redwood noted that the danger of thimerosal-containing vaccines to the unborn child is the primary 

reason only 10% of pregnant women are vaccinated. A large study was conducted with 50,000 women 

over five influenza seasons and showed no difference in influenza or influenza-related illness between 

vaccinated and unvaccinated women. The study also found no difference in vaccinated and 

unvaccinated infants in the first six months of life. The influenza vaccine is a category C vaccine in 

pregnant women, but no safety studies have been conducted to date with reproductive animals.

Ms. Redwood’s position was that the risk of influenza immunization outweighs the benefits. She repeated 

her request for ACIP to state its preference for thimerosal-free vaccines for infants, children and pregnant 

women. She asked ACIP to officially vote on this issue with all members stating their individual 

preferences.

Dr. Schuchat clarified that ACIP is prohibited from voting on any matter without advance notice to the 

public. Because an official ACIP vote on thimerosal-free vaccines was not announced, ACIP would be 

unable to make a decision on this issue during the October 2006 meeting. However, CDC would present 

a systematic update on immunization safety on the following day and would also continue to discuss this 

topic at each ACIP meeting.

Dr. Schuchat could not make a commitment on whether ACIP would officially vote on thimerosal-free 

vaccines during the next meeting in February 2007. In follow-up to Dr. Schuchat’s comments, Ms. 

Redwood announced her intention to notify the media about CDC’s refusal to address thimerosal-free 

vaccines.

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Mr. William Kerry is a parent of an autistic child who is nearly eight years of age. He was aware of 

ACIP’s protocols to officially vote on issues. However, ACIP should publicly acknowledge the significant 

problems with thimerosal-containing vaccines and assure the public that efforts are being made to 

address this issue. This approach would increase the number of individuals who are willing to be 

immunized. Mr. Kerry pointed out that anecdotal evidence showed a decline over the last few years in 

statistical increases in autism in children throughout the state of California. The recent decrease has 

been associated with the voluntary removal of thimerosal from vaccines.

Cmdr. Stephen Kay, of Generation Rescue, is a parent of an autistic child who received >400 μg of 

mercury during his first year of life. Mercury poisoning impacted his son’s ability to detoxify, but chelation 

eliminated all of the physical and metabolic conditions he developed. Cmdr. Kay learned that of 12 

vaccinations on the child immunization schedule, eight still contain thimerosal and one contains 

aluminum. His daughter has never been vaccinated and is healthy. He applauded and appreciated the 

efforts of manufacturers in removing preservatives from vaccines. However, he urged ACIP to formally 

recommend the removal of thimerosal and preservatives from vaccines to regain public trust and 

confidence.

With no further discussion or business brought before ACIP, Dr. Abramson recessed the meeting at 5:55 

p.m. on October 25, 2006.

VACCINE FINANCING

Dr. Abramson reconvened the ACIP meeting at 8:00 a.m. on October 26, 2006 and yielded the floor to 

the first presenter. The series of presentations and ACIP discussion on vaccine financing are set forth 

below.

Dr. Lance Rodewald, Director of the CDC Immunization Services Division, described the current 

immunization program and its stressors; resources that are available to immunization grantees; strategies 

and challenges in implementing new vaccine recommendations; and potential solutions to resolve the 

vaccine financing dilemma. The VFC program is an entitlement to children that mandates funding of 

recommended vaccines. The VFC program was designed to ensure that its implementation would ease 

the use of services and vaccination opportunities would not be missed. A key provision is that VFC 

providers are able to determine individual children’s eligibility to the program. Having a streamlined 

program implementation makes vaccine accountability a critically important challenge to be met by the 

states and by CDC.

ACIP has sole authority in the federal government to add vaccines to the VFC program. ACIP uses 

vaccine safety, efficacy and economic data to make vaccine recommendations. ACIP applies this 

evidence as part of the public health perspective. The methods used in economic studies presented to 

ACIP are now being standardized. However, the Congressional intent and legislative history of the VFC 

program indicated that ACIP would not use cost as the driving force in its public health determinations to 

add particular vaccines to the VFC program, even though cost can be a consideration when ACIP adds a 

vaccine to the VFC program.

At the state level, policies to implement new vaccines are, in part, financed-based. Full access to 

vaccines is expensive and financing gaps exist for underinsured children. States have options to 

Implementation of New Vaccines and Vaccine Recommendations

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ACIP Meeting Minutes October 25-26, 2006 Page 35

implement the VFC program only or implement the VFC program and arrange financing for underinsured 

children at health departments or private immunization providers. Each state has funding sources to 

augment the VFC program, such as its individual appropriated funds or Section 317 discretionary dollars. 

However, Section 317 funds are not an entitlement and have served as a “gap filler” for underinsured 

children in the VFC program over the past 12 years. No restrictions, such as age or insurance status, 

have been placed on using Section 317 program funds. Overall, neither state appropriated funds nor 

Section 317 program funds have kept pace with the VFC needs-based funding. Data showed that the 

VFC program has been able to meet the needs of children compared to the Section 317 program.

States also have an option to use federal vaccine contracts that are negotiated after ACIP passes a VFC 

resolution. States must use the contracts with the VFC program and for Section 317 purchases; states 

may use the federal contracts for state-funded purchases. CDC has prioritized timeliness in the 

negotiation of federal vaccine contracts, but delays have occurred. For example, shipping issues were a 

problem with the varicella vaccine and cost was a concern with the RotaShield vaccine.

CDC is experiencing smaller discounts for newer vaccines. Most notably, federal contract prices for 

vaccines in 2006 included a 51% average discount for vaccines recommended through hepatitis B 

vaccine, but a 17% average discount for varicella vaccine and subsequently recommended vaccines. 

States’ funding accounted for the lowest percentage of childhood vaccine doses purchased in 2005: 46% 

by the private sector; 43% by the VFC program, excluding influenza vaccine; 6% by Section 317 

immunization grantees; and 5% by states.

Data from 1994-2004 showed that the private sector kept pace with the VFC needs-based funding. To 

date, private health insurance typically includes an immunization benefit. Private sector financing is 

largely independent of government purchase policies. Some children have insurance that does not cover 

vaccines and this requires their parents to pay. The 2003 Institute of Medicine (IOM) report estimated 

that 5%-14% of the U.S. childhood population would fall into this category. There are additional 

challenges with private health insurance. Payment for new vaccines might not cover the entire cost of the 

vaccine. A time lag could occur while establishing a code for the vaccine to be included in health 

insurance plans. Private health insurance might exclude some vaccines. Insurance plans that are 

exempt from the Employee Retirement Income Security Act are self-insured and cannot be regulated or 

mandated by states.

The cost of vaccines is one of the most significant stressors of the immunization program. For example,

the federal contract price for vaccines that ACIP universally recommended increased from $45 in 1985 to 

$894 in 2006. In terms of the development of new vaccines, biotechnological advances and 

characteristics of the VFC program are the two primary drivers. For example, the VFC program was 

designed to achieve the “Childhood Immunization Initiative” goal of fostering the development of new and 

better vaccines. ACIP is a committee of independent scientific experts that passes VFC resolutions and 

admits vaccines to the VFC program. ACIP’s VFC resolutions guarantee a substantial market and its 

universal recommendations become national objectives under the Healthy People initiative. Uncapped 

prices for vaccines with new biologics license numbers were established as incentives for manufacturers 

in terms of research and development, funding and profit.

A two-tiered state vaccination policy within local health departments is the major challenge in 

implementing the VFC program. Health department clinics traditionally vaccinated any child who 

presented for immunization, but underinsured children are ineligible for VFC vaccines except at ~3,000 

federally qualified health centers (FQHCs) and rural health centers (RHCs). The VFC program 

designated FQHC and RHCs as “safety net” providers for underinsured children. With this approach, 

state funding and Section 317 dollars would be used to vaccinate underinsured children. However, many 

states could not purchase vaccines for underinsured children due to inadequate state funding and Section 

317 dollars. This process has resulted in a two-tiered policy in which vaccines purchased by the 

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ACIP Meeting Minutes October 25-26, 2006 Page 36

government would not be available to underinsured children at health department clinics. Therefore, 

access to new vaccines for some children is based on insurance status, which creates an ethical tension 

for public health officials, providers and states.

 

States are challenged by having to implement vaccines in an environment where needs are greater than 

resources. For example, states are required to implement the VFC program. A minimum time between 

implementation of ACIP’s VFC resolutions and establishment of federal vaccine contracts for states to 

implement a new ACIP VFC resolution has not been established. The non-VFC population is a significant 

concern due to the cost of new vaccines, underinsured children and adult priority populations. 

Immunization programs in states and urban areas are placed in difficult situations of identifying priorities. 

CDC and ACIP have not prioritized one vaccine over another at this time. States typically prioritize 

immunizations by vaccine rather than populations, but prioritization based on geography and needs might 

be an option.

Data from a survey administered in 2003 showed that 20 states were unable to administer pneumococcal 

conjugate vaccine (PCV) to underinsured children in health department clinics due to two-tiered polices. 

A study was also conducted on state decision-making in vaccination. The data showed that the provision 

of vaccines by grantees in 2006 to underinsured children varied based on geography and specific type of 

vaccine. A review of vaccine purchase data from the Section 317, VFC and state programs in 2005 

showed that health department clinics did not purchase PCV7 vaccine for underinsured children in nine 

states or MCV4 vaccine for underinsured children in 31 states. These states might not have a public 

health department safety net to vaccinate underinsured children against these diseases.

Dr. Rodewald drew three conclusions. First, the safety net for childhood vaccines is severely challenged 

by difficulties providing vaccines to underinsured children. Second, this problem goes beyond the desire 

for a medical home for primary care. Ideally, providers should be able to provide vaccines in the context 

of comprehensive primary care, but failing that, it would be important to at least have a relatively 

convenient location to refer a child with financial barriers. The current situation is such that there are 

areas in the country in which a private provider has no other provider to refer an underinsured children for 

free vaccination. Third, the current implementation of ACIP recommendations as a “patchwork quilt” 

among states for underinsured children is troubling.

Dr. Rodewald noted that several groups in addition to ACIP are attempting to identify solutions to the 

vaccine financing dilemma. IOM published a report on financing vaccines in the 21st century. The 

National Vaccine Advisory Committee (NVAC) formally responded to the IOM report and established a 

Vaccine Financing Workgroup to specifically address this issue. The President’s VFC legislative proposal 

of 2003 included health department clinics as safety net providers for the VFC program. The AAP 

Immunization Task Force is currently focusing on vaccine financing issues.

Dr. Gary Freed, the NVAC Chair, presented an overview of the NVAC Vaccine Financing Workgroup. 

The purpose of NVAC is to advise and make recommendations to the Director of the National Vaccine

Program and the Assistant Secretary for Health. NVAC’s current membership is 17 appointed members, 

including two industry representatives; nine ex- officio members or government agency staff; and six 

liaison members or representatives of other advisory groups. NVAC has no statutory authority, but the 

members raise issues, propose solutions and drive public debate.

NVAC formed its Vaccine Financing Workgroup with three primary charges. A process would be 

established to obtain input from stakeholders. A strategy would be developed to select and address two 

Overview of the NVAC Financing Workgroup

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ACIP Meeting Minutes October 25-26, 2006 Page 37

to three key topics each year. Specific policy options for the key topics would be developed within one 

year. The workgroup is consistent with NVAC’s mandate and defines NVAC’s unique role. Because 

NVAC is not an IOM committee, the workgroup was also asked to establish realistic expectations and 

achievable goals for vaccine financing in the public and private sector in the United States. As a result, 

the workgroup will address incremental changes within the current system rather than systematic 

changes for the entire nation.

The NVAC workgroup is represented by NVAC and NVPO members, CDC and CMS representatives, the 

ACIP Chair and other invited members. During its first face-to-face meeting, the workgroup agreed that 

its focus in the first year would be on private sector, delivery and practice economic issues, such as 

vaccine inventory cost, reimbursement and administration. The workgroup acknowledged the need to be 

mindful of systematic changes in this effort.

The workgroup also identified several action items that would need to be completed in fulfilling its charge, 

such as determining information needs; convening stakeholder panels with industry, private sector and 

public sector representatives; and developing realistic and achievable recommendations to address 

private sector financing issues. The workgroup is now attempting to define the appropriate role of HHS in 

identifying solutions and determine the best venue in addressing comprehensive financing issues.

Dr. Freed emphasized that the workgroup welcomes input from all sources, but all recommendations 

must first be publicly vetted and voted on by the full NVAC membership. Feedback on the workgroup’s 

activities can be submitted to Ms. Angela Shen of NVPO at angela.shen@hhs.gov. 

To guide the discussion on vaccine financing, Dr. Abramson asked for input on short-term actions ACIP 

could take to facilitate full implementation of its vaccine recommendations for children and adults. 

Suggestions by ACIP members, liaisons and other participants in response to Dr. Abramson’s request are 

outlined below.

• ACIP should become involved with ongoing efforts by the AAP Immunization Task Force. 

This group identified three major barriers to practitioners delivering vaccine services to 

the nation: (1) vaccine acquisition costs to private sector physicians; (2) the dilemma 

between administrative fees and the obligation of physicians to provide vaccines to 

patients; and (3) the negative role of vaccine supply issues in actual practice. AAP 

formed three subcommittees to focus on these three issues in more detail, review current 

data and propose potential solutions. However, AAP will convene a stakeholders’ 

meeting in February 2007 to obtain vaccine financing solutions from a broader audience. 

AAP is conducting these activities in parallel with NVAC’s ongoing efforts, but AAP’s 

priorities are somewhat different than the private sector and other constituencies.

• ACIP should become involved with ongoing efforts by the Immunization Workgroup of the 

IDSA National and Global Public Health Committee. This group will soon release a set of 

principles outlining IDSA’s position on overcoming existing barriers and improving the 

delivery of vaccines at all possible visits. IDSA acknowledged that solid coordination 

among ACIP and other groups would assist in strengthening the capacity of current 

systems to deliver vaccines, resolve issues with Section 317 funding, and address 

implementation issues. IDSA is also aware that ACIP and other groups would need to 

coordinate efforts with Congress to enhance state infrastructures, eliminate two-tiered 

systems and minimize inappropriate delivery of vaccines.

• ACIP should become involved with AMA’s ongoing efforts. AMA is attempting to identify 

vaccine financing strategies that could be implemented to allocate Section 317 dollars for 

both adult and pediatric immunizations. AMA made a formal commitment to this activity

by incorporating the improvement of the adult vaccine infrastructure into its three- to fiveyear strategic plan.

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• ACIP and AAP should attempt to reach consensus on extending VFC coverage to 

uninderinsured children.

• ACIP should formally recommend that site visits be made to each state health 

department director in the country due to inadequate state funding of vaccines at the 

local level. This approach might influence and improve the allocation of Section 317 

dollars.

• ACIP should place more emphasis on addressing the need for vaccines in the adult 

population. This issue is an increasing problem, but has not been sufficiently addressed 

by the public sector, private sector or states to date.

• ACIP should assist states in making interim decisions about vaccine implementation.

• ACIP should be involved in ongoing efforts by NVAC, AMA and industry to share 

information and address vaccine financing concerns. For example, several 

manufacturers currently support a 317 coalition that lobbies for additional funding. Under 

this initiative, Section 317 dollars would match needs based on recommended vaccines. 

GSK is supporting a number of studies to measure pediatric vaccine coverage, better 

understand coverage issues and focus on adult immunization funding issues.

• ACIP’s guidance on vaccine financing should focus on a reasonable level of 

reimbursement because this issue is a major consideration within the private insurance 

community.

• ACIP’s guidance on vaccine financing should focus on other basic preventive health 

practices, such as HIV testing and mammograms. This approach might engage other 

preventive health providers who serve populations that are challenged by access to care 

issues and health disparities.

• Guidance on vaccine financing should be provided to state and local immunization 

programs, but ACIP might not serve as the best source for these recommendations. For 

example, ACIP guidance on prioritizing vaccines might minimize the strength of the 

recommendations and cause insurance companies to deny coverage of vaccines.

• ACIP’s guidance on vaccine financing should strongly emphasize the tremendous 

amount of dollars that have been saved in preventing disease from mumps, measles, 

invasive pneumococcal disease and Hib meningitis. ACIP’s recommendations on the 

rising cost of vaccines should be balanced with vaccine cost-savings. This information 

should be presented to legislators and policymakers to encourage adequate funding of 

both pediatric and adult vaccination programs.

• ACIP’s guidance on vaccine financing should acknowledge adverse outcomes that have 

occurred at the local level as a result of “flat funding” of the Section 317 program, such as 

decreased dollars, less staff, no safety net, an inability to deliver vaccines, and a total 

erosion of services. ACIP should provide national leadership in addressing these local 

issues.

Dr. Abramson acknowledged the diversity in the suggestions on short-term actions ACIP could take to 

facilitate full implementation of its vaccine recommendations for children and adults. As a result, he 

confirmed that ACIP would monitor the ongoing efforts of NVAC and other groups in addressing the 

vaccine financing dilemma.

Dr. Abramson announced that CDC would provide ACIP with additional data on use of the zoster vaccine, 

but the presentation would be for informational purposes only and would not require a vote. Dr. Harpaz 

reported that guidance on dosage and administration of the zoster vaccine was extracted from the 

package insert. An assessment of a history of chickenpox was not required for routine vaccination for 

Guidance on Use of Zoster Vaccine [continued]

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ACIP Meeting Minutes October 25-26, 2006 Page 39

adults >60 years of age. Details were provided on simultaneous and non-simultaneous vaccination with 

other adult vaccines.

Routine vaccination of adults >60 years of age should include persons with chronic medical conditions. 

Zoster vaccine should be offered at the first clinical encounter. Strategies to ensure vaccination should 

include linkages to other adult vaccines and preventive services. Emphasis should be placed on solid 

adult vaccine delivery practices. Residents of chronic care facilities should be included in vaccination 

efforts as appropriate. A permanent vaccine record should be maintained for both providers and patients.

Guidance on vaccine storage and handling was extracted from the package label. Unreconstituted 

vaccine should be discarded if the temperature exceeds 5°F. Providers should take measures to prevent 

inadvertent freezing of refrigerated vaccine kept in combined refrigerator units. Providers should call the 

manufacturer’s hotline to request additional information on storage and handling.

The challenges of vaccine safety monitoring in the target population were emphasized, particularly the 

high rate of medical events in older persons. Zoster vaccine is the first live vaccine that was specifically 

developed for the elderly. Guidance was provided on administration errors and infection control practices 

for shingles. The zoster vaccine was not recommended for the sole purpose of preventing household or 

occupational VZV transmission.

Guidance was provided for specific populations: (1) persons receiving blood products or antiviral 

medications that could interfere with VZV transmission; (2) persons with a history of varicella vaccine; (3) 

nursing mothers; and (4) vaccinees with household members at high risk for attenuated VZV. No 

indications were established for use of zoster vaccine to control or prevent current shingles or PHN 

cases. Allergies to vaccine components and pregnancy were highlighted as contraindications to 

vaccination, while severe illness and active untreated tuberculosis were noted as precautions to 

vaccination.

MENINGOCOCCAL VACCINE

The series of presentations and ACIP discussion on the meningococcal vaccine are set forth below.

Dr. Carol Baker, the Meningococcal Workgroup Chair, highlighted the workgroup’s three major 

recommendations. First, administration of MCV4 should be continued for adolescents 15 years of age, 

freshmen entering college who will live in dormitories, and persons at increased risk of invasive 

meningococcal disease. Second, routine MCV4 immunization of adolescents 11-12 years of age should 

be resumed. Third, CDC should initiate active surveillance studies of vaccine-associated GBS.

The workgroup based its original recommendations on two major factors. Increased rates of 

meningococcal disease per 100,000 population in serogroups A, C, Y and W135 are observed in persons 

11-30 years of age, but sanofi pasteur indicated that MCV4 supply would not support immunization of all 

adolescents aged 11-18 years. Thus, the workgroup prioritized three cohorts for MCV4 immunization. A 

three- to five-fold increase was observed in college freshmen living in dormitories. Surveillance data 

showed a peak in meningococcal disease among persons 15-18 years of age. The adolescent platform 

at 11-12 years of age would be important because this population typically presents to physicians for 

immunization and other preventive services. During the meeting, the workgroup presented updates on 

Overview

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ACIP Meeting Minutes October 25-26, 2006 Page 40

the MCV4 supply, the occurrence of GBS in recipients of MCV4, and a decision analysis to support its 

recommendations.

Dr. Wallace reported that the high demand of MCV4 in June 2005 resulted in order limits and back orders 

in both public and private sectors. The demand initially was highest among college freshman. CDC 

emphasized its initial recommendations for vaccination only of three distinct cohorts. A high demand 

occurred in the summer following approval of MCV4, but complaints and concerns about supply rapidly 

diminished in the fall and winter. In year 1, sanofi pasteur distributed ~4.1 million doses and projected 

that ~6 million doses would be distributed in year 2.

CDC convened a Supply Workgroup with representation by ACIP, CDC, other federal agencies, sanofi 

pasteur and professional organizations. CDC also published a notice in the May 19, 2006 edition of the 

Morbidity and Mortality Weekly Report (MMWR) to alert readers to the limited supply of MCV4 and 

recommend deferring vaccination of persons 11-12 years of age. Insurance claims data collected 

through March 26, 2006 confirmed MCV4 use across all adolescent ages, not just the recommended 

cohorts. However, it appeared that CDC’s revised guidance on Menactra® significantly impacted 

vaccination practice among physicians because use in 11-12 year olds was greatly reduced after the May 

MMWR report.

The distribution of cumulative doses has steadily increased since CDC issued its revised 

recommendations. Data on the number of doses distributed each month from March 2005 to September 

2006 demonstrated diligent efforts by sanofi pasteur to distribute as many doses as possible during the 

summer demand. In terms of the future supply, sanofi pasteur is meeting its projections for 3.5-4.5 million 

additional doses through March 2007. Back orders have been filled and restrictions were released on 

order sizes for the private sector. CDC will collaborate with sanofi pasteur to ease the caps placed on 

order sizes in year 1 for the public sector.

Dr. Wallace asked ACIP to consider the following issues during its discussion. Significant doses are 

projected to be available in the future. Adolescents 17-18 years of age likely received a larger proportion 

of vaccine in year 2 compared to year 1, likely at least partially due to the revised recommendations. The 

Supply Workgroup has determined that supply is now adequate to return to routine recommendations. 

An article the workgroup developed is ready for publication in the November 3, 2006 edition of the 

MMWR. Pending the outcome of the current ACIP meeting, the workgroup will coordinate with partners in 

publishing the announcement to return to routine recommendation.

Dr. Robert Davis, Director of the CDC Immunization Safety Office (ISO), reported that GBS is a serious 

neurologic disorder involving inflammatory demyelination of the peripheral nerves. Additional cases of 

GBS after MCV4 vaccination continued to be reported to VAERS following the April 2006 MMWR article. 

CDC assessed the reports to determine whether the new cases indicated an increased risk for GBS after 

MCV4 vaccination. Three articles were published in the MMWR on 17 GBS cases after MCV4 

vaccination reported to VAERS from October 2005 to October 2006.

A CDC medical officer and an independent clinical immunization safety assessment investigator reviewed 

the nine most recent cases reported to VAERS in October 2006. Both reviewers confirmed diagnoses of 

Update on the MCV4 Supply

Overview of GBS in MCV4 Recipients

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ACIP Meeting Minutes October 25-26, 2006 Page 41

GBS in all nine cases. Eight of the nine cases met the surveillance case definition. The remaining case 

was a sensory variant of GBS that was diagnosed by an attending neurologist and was based on nerve 

conduction studies consistent with GBS. A case review showed that clinical data for other causes of GBS 

typically were not available. Campylobacter jejuni (C. jejuni) is the leading cause of gastroenteritis and is 

also the most frequent antecedent pathogen in GBS cases.

Of all 17 GBS cases, none reported diarrheal prodromes; three had stool cultures taken; and two tested 

negative for C. jejuni based on either a stool culture or serum sample. None of the states where the 

patients resided reported outbreaks of C. jejuni from June 2006 to September 2006. No evidence was 

seen of geographic clustering. The onset of the 17 cases ranged from 2-33 days following vaccination. A 

temporal scan statistic showed a significantly elevated risk for clustering in the period of 9-15 days 

following vaccination. Data from a managed care organization (MCO) within the Vaccine Safety Datalink 

(VSD) indicated that ~94% of persons who received MCV4 vaccination were 11-19 years of age. As a 

result, subsequent analyses were limited to this population and excluded two GBS cases in persons 30 

and 43 years of age.

The analysis was designed to determine whether the reporting rate for GBS after MCV4 vaccination was 

higher than expected. Variables input into the calculation included observed, background and expected 

reporting rates. The analysis was based on several assumptions, including that all cases were reported 

and that all vaccine distributed was, in fact, administered. The analysis suggested that there might be 

a small increased risk of GBS after MCV4 vaccination. The timing of neurologic symptoms within one to 

five weeks of vaccinated cases is a concern. 

Risk estimates using background incidence rates from either VSD or the Healthcare Cost and Utilization 

Act have substantial uncertainties. The completeness of GBS reporting to VAERS is unknown. Underreporting of GBS after MCV4 vaccination would increase risk estimates. The absence of any GBS cases 

after MCV4 vaccination in persons 11-19 years of age would not offer substantial reassurance regarding 

MCV4 safety.

On the other hand, no surge in GBS cases reported to VAERS was seen after publication of the MMWR

articles. Overall, the VSD has limited ability to detect rare adverse events. A larger study would be 

needed to provide a more definitive assessment, but this research would require several years to 

accumulate cases and attain sufficient statistical power. An evaluation of GBS cases after MCV4 

vaccination is underway within VSD.

The additional cases reported do not affect or change CDC’s current recommendations due to the 

ongoing risk for meningococcal disease 

Dr. Bo-Hyun Cho, of CDC, presented preliminary findings from a cohort simulation model that was 

developed to compare health outcomes of vaccination and no vaccination in the presence of GBS risk. 

The hypothetical birth cohort included 4.1 million adolescents 11 years of age who were followed over an 

eight-year period. The patient perspective was considered in the study. Outcome measures included 

cases of meningococcal disease and GBS, death and life-months lost, and quality adjusted life months 

(QALMs).

The study was based on several assumptions. GBS and meningococcal disease would be independent 

and mutually exclusive events. Only meningococcal disease vaccine-preventable serogroups would be 

considered. A six-week risk window would be used for vaccine-attributable GBS. The life expectancy of 

adolescents would be 67.7 years of age. The probability of a vaccine-attributable GBS episode was 

Decision Analysis of Meningococcal Disease Vaccination in the Presence of GBS

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ACIP Meeting Minutes October 25-26, 2006 Page 42

calculated with the frequency of GBS episodes among vaccinated persons reported to VAERS and the 

baseline risk for GBS among unvaccinated persons with data from VSD.

Several parameters were input into the model. A 5% morbidity rate among adolescent GBS patients was 

used based on a published study. Vaccine efficacy was assumed to be 93%. An incidence rate of 

0.77/100,000 was used for meningococcal disease among unvaccinated persons based on unpublished 

data. The meningococcal disease incidence rate among vaccinated persons was scaled down by 1 

minus vaccine efficacy. The vaccine coverage rate was assumed to be 70%. A 10% case fatality rate 

was used based on unpublished data. The health utility index (HUI) of long-term disability related to GBS 

was 0.698 based on a published study. The HUI of survival for meningococcal disease was 0.952 based 

on both published and unpublished data.

Preliminary findings from the study are as follows. MCV4 vaccination would prevent 163 meningococcal 

events and 16 deaths associated with meningococcal disease in a cohort of 4.1 million. Three cases of 

vaccine-attributable GBS cases would occur. GBS would cause 37 QALMs lost. Vaccination would 

prevent 12,488 life months lost and 5,352 QALMs lost.

The following results were seen when the case fatality rate was changed to 20% and the GBS morbidity 

rate was changed to 10%: (1) an increase from 16 to 32 deaths associated with meningococcal disease; 

(2) an increase from 12,488 to 24,976 life months lost; (3) a decrease from 5,352 to 4,757 QALMs lost; 

and (4) an increase from 37 to 85 QALMs lost caused by GBS. Overall, the cohort simulation model 

showed that MCV4 vaccination is favorable. The period of an increased risk of vaccine-attributable GBS 

is limited, while the benefit of meningococcal disease prevention is prolonged.

CDC made several remarks in response to ACIP’s request for clarification on the analysis of GBS among 

MCV4 recipients and the preliminary findings from the cohort simulation model of meningococcal disease 

vaccination in the presence of GBS. However, Dr. Davis emphasized that many of the questions could 

not be answered at this time because the data are preliminary.

Two key comments were made for the workgroup to consider in its ongoing focus on meningococcal 

vaccine and vaccine-associated GBS. Dr. Allos advised the workgroup to cautiously consider results of 

the two patients who tested negative for Campylobacter because bacteria were not isolated from stool 

cultures. For example, persons infected with Campylobacter typically excrete bacteria in their stool for a 

median of 16 days. Most persons who develop GBS following Campylobacter have an onset of 

symptoms at 10-21 days after infection. Due to time lags between the individual seeking medical care 

and the provider ordering a stool culture, Campylobacter would not be detected in stools of GBS patients 

even if Campylobacter was the trigger.

Dr. Michael Decker, of sanofi pasteur, was pleased to announce that progress is being made on the 

workgroup’s request for active surveillance studies of vaccine-associated GBS. A traditional case-control 

study would be virtually impossible to conduct because VSD is not nearly large enough to undertake a 

research project of this magnitude. Collaborations are underway between sanofi pasteur and a VSD 

contract site to coordinate and markedly expand VSD, launch an enormous cohort study, and address 

vaccine-associated GBS and other issues in the future. CDC, FDA and a number of other groups are 

also involved in this effort. At least two years would be required to collect a sufficient amount of data for 

the large cohort study, but the research partners expect to implement a study protocol within the next few 

months.

Summary. After the above presentations and discussion, Dr. Baker summarized the workgroup’s 

recommendations to resume routine use of MCV4 in 11-12 year olds, to continue MCV4 use in previously 

recommended cohorts and those at increased risk of meningococcal disease, and to conduct additional 

research into the possible increased risk of GBS in MCV4 recipients.

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ACIP Meeting Minutes October 25-26, 2006 Page 43

Dr. Davis reported that CDC is conducting safety monitoring planning for all new vaccines to facilitate 

transparency and accountability, promote consistency of safety profiles, and document existing 

processes. CDC undertook this effort due to existing or pending approval of new vaccines or indications 

for rotavirus, shingles, HPV, MMRV, meningococcal disease, Tdap and influenza.

CDC will develop a safety profile for each new vaccine with two primary modes of data collection. First, 

VAERS is a passive surveillance system with capacity to provide signal detection and the potential for 

reporting from the entire United States. However, the limited, variable, biased and still primarily paperbased VAERS reporting system does not provide epidemiologic data. Diligent efforts are being made to 

promote an existing web-based system and make other improvements in VAERS. Second, VSD is an 

active surveillance system that collects data from eight health maintenance organizations (HMOs) or 3% 

of the United States. VSD captures highly complete outcomes and provides epidemiologic data, but has 

limited power for very rare adverse events.

For intussusception and other serious gastrointestinal reports, CDC and FDA review VAERS reports on a 

daily basis. The daily summaries include information on severity of the adverse event, age at vaccination, 

onset interval in days between vaccination and symptoms, gender of the vaccinee, all vaccines 

administered, pre-existing medical conditions and known allergies. For serious reports, VAERS nurses 

obtain radiologic, surgical or autopsy information with medical records confirmation. A Brighton case 

definition is used to verify suspected intussusception reports. Reporting rates are calculated and 

compared to background rates. The percent of COSTART codes are compared in children <12 months of 

age. For example, RotaTeq® and other vaccines are compared to children of the same age who 

received the same vaccines without RotaTeq®.

CDC uses VSD for safety monitoring because other than VAERS, no routine surveillance system has 

been developed to monitor vaccine safety signals in the United States. Recent events underscored the 

need for more timely reporting systems that are able to detect adverse events as closely as possible to 

real time following the introduction of new or modified vaccines, such as myocarditis associated with the 

smallpox vaccine, intussusception associated with the rotavirus vaccine, and Bell’s palsy associated with 

the influenza vaccine.

The primary goals of CDC’s rapid cycle analysis (RCA) conducted within the VSD are to detect adverse 

events associated with newly introduced vaccines and monitor adverse events arising with changes in 

established vaccines. However, the RCA system serves as a denominator-based assessment of whether 

future investigations would be needed rather than a final answer to an epidemiologic question. CDC 

collects information on all known vaccinees each week and follows each individual for a six-week 

observation period. The rate of adverse events is analyzed in the cohort of vaccinees and compared to 

either a comparison group or historical background rates. A fairly sophisticated statistical analysis is 

developed each week to determine the presence or absence of a signal for an adverse event compared 

to historical background rates.

CDC will use VAERS as a front-line monitoring system for gastrointestinal and other unexpected vaccine 

adverse events related to RotaTeq®. CDC will also incorporate the RCA system into VSD to conduct a 

real-time assessment of gastrointestinal-related vaccine adverse events among children 2-12 months of 

age who received RotaTeq®. Rates of intussusception and other serious gastrointestinal conditions will 

be analyzed and compared to historical rates. VSD will be used to confirm additional unexpected VAERS 

signals.

ISO Update

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ACIP Meeting Minutes October 25-26, 2006 Page 44

Ms. Penina Haber, of ISO, summarized recent RotaTeq® vaccine events that were reported to VAERS. 

As of September 30, 2006, ~1.7 million RotaTeq® doses were distributed. Of 189 RotaTeq® vaccine 

events reported to VAERS from March 1-October 23, 2006, 48% were from RotaTeq alone; 61% were

after the first dose; 34% did not indicate the number of doses; 57% were among children 2-3 months of 

age; 5% were among children <2 months of age; 55% had an onset of symptoms within 0-2 days; 5% had 

an onset of symptoms within 3-7 days; and 16% had intussusception or other serious adverse events.

The most frequent adverse events following RotaTeq® vaccination in children 0-12 months of age were 

diarrhea in 24%, vomiting in 22% and fever in 17%. Six intussusception cases were reported to VAERS 

with a range in age of 4-21 weeks and a range in the interval of symptoms of 2-32 days. Of the six cases, 

four had surgery, two had necrotic bowel resection, and four developed intussusception after the first 

dose. No deaths have occurred. 

To estimate intussusception risk, CDC obtained VSD data from 2000-2004 and used an average 

background rate in children 6-32 weeks of age. The risk was calculated at 2.98 intussusception cases 

per 10,000 person-years. The expected number of cases within 21 days after vaccination at any dose 

was estimated to be 30.7. The observed risk within 21 days was four intussusception reports per ~1.7 

million persons. CDC used published data to assume a 47% under-reporting rate. The observed 

frequency of ~8.51 in the four observed cases was statistically significantly lower than the expected 30.7 

cases even after adjusting for under-reporting.

CDC also formed an Intussusception Workgroup to systematically collect clinical data, demographics on 

intussusception cases, and stool, serum and tissue samples. The workgroup members had expertise in 

VAERS, rotavirus disease epidemiology, and pathology and virology laboratory procedures. The 

laboratory specimens were tested for wild-type and rotavirus vaccine strains and adenovirus. Specimens 

were requested on all intussusception reports regardless of the time since vaccination.

The results of three cases in which intussusception specimens were obtained are as follows. The ages of 

vaccinees were 11 and 12 weeks at dose 1 in cases 1 and 2, respectively, and 16 weeks at dose 2 in 

case 3. Necrotic bowels were resected on day 8 and 16 in cases 1 and 2, respectively, and the bowel 

was reduced in case 3. Tissues were negative for rotavirus and adenovirus in case 1; tissue results are 

pending in case 2; and stool and serum results are pending in case 3. The stool sample in case 1 

revealed a VP4 gene that was identical to the rotavirus vaccine strain.

Reports of 19 hematochezia cases, excluding intussusception, were also submitted to VAERS among 

children 1-12 months of age after RotaTeq® vaccination. CDC and FDA agreed to characterize 

“hematochezia” as bloody diarrhea, melena, or colon, gastrointestinal or rectal hemorrhage. Of the 19 

hematochezia reports, 37% were after receipt of RotaTeq® only; 68% were made within three days of 

vaccination; and 68% were among children two months of age. A comparison showed that the 19 

hematochezia reports were per 1.7 million RotaTeq® doses distributed, while 60 hematochezia reports 

were per 1.5 million Rotashield® doses distributed. For other vaccines in the same time period and with 

the same age group, four hematochezia reports were submitted among 2,248 total reports.

Preliminary results of the RotaTeq® reports submitted to VAERS are as follows. Few serious cases after 

RotaTeq® were observed when the vaccine was used alone. Intussusception reports were less than the 

expected rate in the general population. Hematochezia reports were primarily within three days of 

vaccination, but none of these events were serious. Overall, CDC acknowledges that these findings are 

subject to limitations of passive surveillance systems.

CDC is using its VSD RCA system to conduct an observational study of RotaTeq® in eight sites that 

capture ~96,000 births per year. The primary events that will be analyzed in the study include 

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ACIP Meeting Minutes October 25-26, 2006 Page 45

intussusception, gastrointestinal bleeding, meningitis, encephalitis, seizures, gram-negative sepsis, and 

other signals which may be identified through VAERS. During post-marketing and other follow-up 

activities for RotaTeq®, CDC will obtain additional data from Merck’s Phase IV study of ~45,000 children 

and will continue to convene conference calls with FDA and the manufacturer to coordinate the research 

projects.

Dr. Davis provided an update on ISO’s efforts in developing a comprehensive immunization safety 

research agenda in an open and transparent process with both extensive internal and external input. 

This activity was triggered by the release of the IOM Vaccine Safety Research, Data Access and Public 

Trust report in February 2005. The entire report included 28 recommendations on vaccine safety 

research, public access to vaccine safety data and public trust, but Chapter 5 was specifically devoted to 

an independent review of VSD activities. Chapter 5 noted that “the limited ability of independent external 

researchers to conduct high-quality corroboration studies or studies of new hypotheses create a special 

need to involve the public in the priority setting process for the VSD research plan.”

Chapter 5 also contained specific recommendations. An NVAC subcommittee should be formed with a 

wide variety of stakeholders to review and provide advice on the VSD research plan. The existing Safety 

and Communications Subcommittee could serve as the new NVAC subcommittee. Subcommittee 

meetings should be public to allow interested persons to observe the process and provide input through 

established mechanisms.

In response to the IOM report, CDC will develop a comprehensive safety research agenda with both 

internal and external input. Transparency, standardization and credibility will serve as the guiding 

principles of the research agenda. The focus and strengths of the research agenda will be to leverage 

partnerships, invite extensive internal and external collaborations, facilitate efforts with NVAC, produce 

scientific credibility, and promote public trust.

CDC and Merck made several comments in response to ACIP’s questions on safety monitoring of 

RotaTeq®. First, CDC will use VSD to encourage MCOs to adhere to ACIP’s age-based 

recommendations on RotaTeq® vaccination in the immunization schedule. CDC is aware that ACIP 

issued this guidance due to its concern about the association between age and intussusception. 

Second, CDC will correct the ISO data that showed an infant four weeks of age received a second 

RotaTeq® dose. The infant was actually six months of age at the time of the second dose. Third, efforts 

are underway at Merck that are parallel to CDC’s activities on safety monitoring of RotaTeq®. For 

example, Merck is reviewing data from insurance claims and HMOs to determine the actual use of 

RotaTeq®, specific age groups that are receiving the vaccine, and turnover in use of the vaccine by 

practice.

HPV VACCINE

The series of presentations and ACIP discussion on the HPV vaccine are set forth below.

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Dr. Lauri Markowitz, of CDC, announced that ACIP’s provisional recommendations on the quadrivalent 

HPV vaccine were posted on the CDC web site shortly after the June 2006 ACIP meeting. The ACIP 

statement is currently undergoing the CDC clearance and Office of Management and Budget review 

processes. CDC expects the statement to be published in the first half of 2007.

The catalog price of the quadrivalent HPV vaccine is $120/dose. ACIP adopted a VFC resolution for the 

vaccine during the June 2006 meeting; the VFC contract is still being negotiated. Data from the 

manufacturer showed that 750,000 doses were distributed through mid-October 2006. As of the end of 

September 2006, 76 adverse events were reported to VAERS with the manufacturer serving as the 

source of 74% of these reports. Of the 76 reports, 42% were among persons 11-18 years of age; 2 were 

among males; 86% involved quadrivalent HPV vaccine only; and 50% involved adverse events with onset 

the day of vaccination.

The five most frequently reported symptoms after quadrivalent HPV vaccine was syncope, pain at 

injection site, rash, dizziness and fever. Three serious reports were reported to VAERS after HPV 

vaccination in females 14 and 16 years of age. One of these patients had vasovagal syncope and was 

hospitalized overnight for observation. Two patients who received MCV4 at the same visit as HPV 

vaccination developed GBS. Merck established a vaccine in pregnancy registry. No outcomes have 

been reported to date. There have been nine exposures during pregnancy and seven persons were 

enrolled in the registry.

CDC will monitor coverage of the quadrivalent HPV vaccine. The National Immunization Survey (NIS) will 

use its sample frame methodology to conduct a teen module in October-December 2006 through a 

random digit dial telephone survey. The national sample will include ~5,000 parents of teens 13-17 years 

of age. Initial data will be available in June 2007. The survey will include questions on specific vaccines, 

HPV and HPV vaccine knowledge, reasons for not receiving new vaccines, health insurance, VFC 

eligibility, and the adolescent visit at 11-12 years of age. Provider records will be checked to verify 

immunizations.

NIS will also conduct an adult module in the second quarter of 2007 through a telephone interview of 

adults 18-49 years of age. The survey will include questions on HPV and other recommended 

vaccinations. Provider records will not be checked to verify immunizations. Results of the adult module 

will be used to guide questions on the 2008 National Health Interview Survey.

The National Survey of Children’s Health will provide national and state-based estimates. This survey 

was conducted in 2003 and will be repeated in 2007. The national sample of ~102,000 children will 

include ~2,000 children <18 years of age per state. Household interviews will be administered to ~20,000 

teens 13-17 years of age. The survey will include questions on HPV, Tdap and meningococcal vaccines. 

Immunization data will be based on parental recall only.

The Immunization Information System sentinel sites will conduct an adolescent registry model in 

geographically limited areas in five states and the District of Columbia. Quarterly data will be collected 

from the third quarter of 2006 to the fourth quarter of 2007. Coverage estimates will be gathered on 

individual vaccines, vaccine series recommended for adolescents, and concomitant administration of 

recently recommended vaccines.

The Association of Immunization Managers (AIM) administered a web-based survey in September 2006 

to its 64 grantees to identify strategies that would be used to implement HPV vaccine. Of 44 grantees 

that responded to this question, 20 planned to provide HPV vaccine to VFC-eligible females 11-12 years 

Update on the Quadrivalent HPV Vaccine

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ACIP Meeting Minutes October 25-26, 2006 Page 47

of age only; 23 planned to provide vaccine to females in the age groups of 9-18, 11-12, 11-14, 11-18 or 

17-18 years; and 1 had no plans at the time of the survey to purchase vaccine.

AIM acknowledged several reasons for grantees providing age ranges for HPV vaccination that were 

more limited than ACIP’s recommendations. Grantees were concerned about the limited inventory of 

HPV vaccine when the VFC contract initially would be established. Most states have no interest in 

developing a two-tiered system if funds through other sources would be insufficient for vaccine 

purchases. States would limit the number of cohorts to ensure that vaccine would be available to all 

persons within a limited age group. States would fully implement the HPV vaccine recommendations 

when funding was identified.

Of 44 grantees that responded to this question, 14 would provide HPV vaccine to underinsured females 

11-12 years of age in public settings; 16 planned to provide vaccine to females in the age groups of 9-18, 

11-12, 11-14, 11-18 or 17-18 years; and 13 had no plans at the time of the survey to purchase vaccine. 

Of 41 grantees that responded to this question, 30 had no plans to purchase HPV vaccine for females 19-

26 years of age and only 6 had plans to purchase vaccine through either Section 317 dollars or state and 

local funds. However, 17 grantees planned to educate providers or consumers about the vaccine.

Dr. Markowitz announced that the HPV Vaccine Workgroup would continue to review data on both the 

bilavent and quadrivalent HPV vaccines. GSK recently reached the pre-specified number of events in the 

Phase III trial and plans to submit a BLA to FDA in the spring of 2007. The ACIP statement would be 

revised as needed based on new data that become available

Dr. Eliav Barr, of Merck Research Laboratories, presented data from clinical studies on the disease 

burden and efficacy of the GARDASIL® quadrivalent HPV recombinant vaccine in North American 

women. The U.S. population contains a mixture of naive, partially exposed and fully exposed women. 

“Naive” women are naive to all four vaccine HPV types and would derive maximum benefit from 

vaccination. “Partially exposed” women have ongoing or prior infection with <4 vaccine HPV types and 

would derive some benefit from vaccination.

Clinical studies of the GARDASIL® prophylactic HPV vaccine included 5,996 North American women 16-

24 years of age. The number of lifetime sexual partners was restricted to <6 in the Phase IIa trial and <5 

in the Phase IIb/III trial. Virginal adolescents 16-17 years of age were excluded from the study. Subjects 

from 35 states, Puerto Rico and three Canadian provinces were enrolled in the study. Most of the sites 

were on college campuses, but several sites were in inner city settings. The study focused on the 

primary outcome of prophylactic efficacy of the vaccine in baseline HPV-naive subjects. Additional 

analyses were done to focus on the secondary outcome of the impact of the vaccine in the general 

population regardless of baseline HPV status. The current follow-up period of the study is 2-4 years.

Key demographics of the North American cohort of 5, 996 subjects are as follows: the median age was 

20 years; 73.4% were white; 15.4% had a pregnancy history; 92% were non-virgins; the mean age at first 

sexual intercourse was 16.9 years; 9.6% self-reported a history of sexually transmitted infections; and 

13% had a previous Pap test abnormality. The sexual behavior of the cohort was compared to data from 

the National Survey of Family Growth (NSFG). In NSFG, 77% of women 15-24 years of age were 

sexually active (compared with 92% in the North American cohort in the vaccine trial). Among those 

sexually active, the median number of sexual partners was 2 (similar to those in the vaccine trial).

Overview of the GARDASIL® Population Impact Analysis

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In the North American cohort, the prevalence of chlamydia was 3% and the prevalence of gonorrhea was 

0.4%. Of 3,587 subjects with serology or PCR test results for HPV types 6/11/16/18, 76.1% were naive to 

all four types; 23.9% were positive to 1 or more types; and 0.1% were positive to all four types. Few of 

the subjects >23 years of age were positive to both HPV types 16/18. Even if seroprevalence is assumed 

to be double what was detected, to account for the fact that not everyone develops antibody after 

infection, a small percentage would have been positive for both HPV types 16/18.

Data from the clinical trials showed several major findings. Most women 16-24 years of age with multiple 

sexual partners remained naive to at least one of the two cancer causing HPV types. Among women who 

were positive to one HPV type, prophylactic efficacy against the other types to which they were naive 

remained high at ~90%. Prophylactic efficacy was not impacted by the presence of at least one positive 

vaccine HPV type at baseline.

In the North American cohort general population analysis, including all women regardless of HPV status, 

the proportion of women in the vaccine group with HPV 16/18-related cervical intraepithelial neoplasia 

(CIN) 2/3 or adenocarcinoma in situ (AIS) was reduced by 67% compared with the placebo group. In the 

same population, the proportion of women in the vaccine group with any CIN 2/3 or AIS lesions was 

reduced by 32% compared with the placebo group. The benefit of the vaccine became more apparent 

over time as prevalent disease was identified and resolved and incident disease was prevented. Merck 

will continue to conduct analyses in Phase III studies to collect data on the overall population impact of 

the vaccine on rates of CIN 2/3 and type-specific disease.

Dr. Barr summarized the major conclusions based on data from the GARDASIL® clinical studies. In the 

general population of North American women 16-24 years of age, most subjects were naive to all four 

vaccine HPV types and few subjects were positive to both HPV types 16/18 even with four lifetime sexual 

partners or a Pap test abnormality. Event rates were high in the study population. Administration of 

GARDASIL® would be highly effective in reducing the burden of HPV disease. The benefits of 

GARDASIL® would become more apparent over time.

Dr. Elamin Elbasha, of Merck Research Laboratories, presented data from a study that projected the 

epidemiologic and economic consequences of a quadrivalent HPV vaccine in the United States. An 

integrated disease transmission model (which captured direct and indirect herd immunity effects of 

vaccination) and cost-utility analysis were developed, applying data on demographics, behaviors, and 

HPV infection and disease. U.S. health system data were applied that assumed existing screening 

practices would continue after vaccination

Vaccination strategies examined included vaccination of females before 12 years of age and four 

temporary catch-up programs targeted to females 12-14, 12-17, 12-19 and 12-24 years of age. Vaccine 

characteristics were based on both data and assumptions of vaccine take, vaccine degree and duration of 

protection, and breakthrough infections. Vaccine penetration for routine vaccination of adolescents 12 

years of age was assumed to increase linearly from 0% in year 0 to reach a maximum of 70% in year 5. 

For the temporary catch-up program, the ramp-up among previously unvaccinated females was from 0% 

to 50% over 5 years with a decline to 0% thereafter.

 

Several efforts were undertaken to validate the model. Persons with expertise in the natural history of 

HPV infection and disease were consulted. HPV vaccination and cervical cancer screening models were 

reviewed. Mathematica® was used to program equations and perform all calculations in the model for 

consistency. All of the model equations and inputs were publicly released for review. Several tests were 

Cost-Effectiveness of a Quadrivalent HPV Vaccine in the United States

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performed to establish technical accuracy. The predictive validity of the model was compared to 

predictions of HPV prevalence, genital warts, CIN 1/2/3, and cervical cancer incidence and death in the 

published literature. Several analyses were performed with the model to make the following projections:

• The proportion of females currently or previously infected with HPV types 16/18 by age 

prior to vaccination.

• The incidence of HPV types 6/11/16/18-related CIN 2 by age prior to vaccination.

• The public health impact of various vaccination strategies on HPV types 16/18-related 

cervical cancer.

• The cumulative incremental impact of vaccination strategies on HPV types 16/18-related 

cervical cancer.

• The impact of vaccination strategies on HPV types 6/11/16/18-related CIN 2/3 among 

females.

• The impact of vaccination strategies on HPV types 6/11-related genital warts among 

males. Although male vaccination was not included in this scenario, a substantial 

reduction in the incidence of genital warts in males would be expected due to herd 

immunity effects and the protection of female partners.

The model was also used to demonstrate additional HPV types 16/18-related cervical cancer cases that 

would be prevented in the United States in the next 25 years. The model suggested that routine 

vaccination of females 12 years of age would prevent 10,124 cervical cancer cases assuming lifelong 

duration of protection.

Catch-up programs targeting females 12-17 years of age would prevent an additional 10,181 cervical 

cancer cases. Expanding the catch-up vaccination to include women 18–19 years of age would prevent 

an additional 3,980 cervical cancer cases. Expanding catch-up beyond age 19 years to include women 

20-24 years of age would prevent an additional 6,134 cases of cervical cancer. The cost-effectiveness of 

various HPV vaccination strategies was analyzed as well. Overall, the strategy of routine vaccination of 

12-year old females plus catch-up vaccination of females 12-24 years of age was found to be the most 

effective strategy at a cost of $10,362 per QALY.

Dr. Elbasha summarized the major conclusions of the cost-effectiveness study of a quadrivalent HPV 

vaccine in the United States. A prophylactic quadrivalent HPV vaccine could be efficiently added to 

current screening programs and also could reduce the incidence of cervical cancer, CIN and genital 

warts. Catch-up vaccination could provide earlier and greater reductions in HPV-related disease. 

Vaccination of females before 12 years of age combined with a temporary catch-up program of females 

12-24 years of age could be cost-effective relative to many other public health interventions.

Dr. Gustavo Dayan, of CDC, provided an update on the mumps outbreak that occurred in the United 

States in 2006. CDC published dispatches in the March 30 and May 18, 2006 editions of the MMWR on 

the unexpected increase in mumps cases in Iowa and the spread of the outbreak to other states. An 

update on mumps activity in the United States from January 1-October 7, 2006 is scheduled for 

publication in the October 27, 2006 edition of the MMWR. 

CDC used two major sources to collect mumps data. Data from cases with dates of onset from January 

1-October 14, 2006 were extracted from the National Notifiable Disease Surveillance System states use 

to electronically report mumps cases to CDC. Data from patients with dates of onset between January 1-

July 31, 2006 were also extracted from databases of seven states with the most mumps cases: Iowa, 

Update on the Mumps Outbreak

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Kansas, Illinois, Missouri, Nebraska, South Dakota and Wisconsin. The outbreak peaked in April 2006 

and began to decrease in May 2006. The number of cases reported by states ranged from 1-1,971 with 

the seven highly affected states reporting >100 cases each. The incidence of mumps also ranged among 

states from 3-67 cases/100,000.

Key demographics of the mumps outbreak in the United States were as follows: 63% female, 90% white, 

93% non-Hispanic, and a median age of 22 years. The ages of the cases ranged from <1-96 years, but 

the age group of 18-24 years was most affected. Parotitis was present in 68% of cases. The G strain 

was isolated from the outbreak and was identical to the G genotype in the mumps outbreak in the United 

Kingdom. Of nearly 6,000 reported cases, 4% were unvaccinated and 46% had received two vaccine 

doses. The vaccination status was unknown in 30% of cases.

CDC followed specific mumps clusters in several states. An Illinois cluster included 85 persons 17-30 

years of age in a college from August 31-October 13, 2006. Ten students had positive immunoglobulin M 

(IgM) results, seven had positive PCR results, 93% had received two vaccine doses, and orchitis and 

myocarditis were each present in one case. A Kansas cluster included 22 persons 18-24 years of age at 

two colleges from August 7-September 22, 2006. Of these students, 95% had received two vaccine 

doses. A Virginia cluster included 24 persons 18-22 years of age and one healthcare worker from 

September 22-October 23, 2006. Of these cases, 96% had received two vaccine doses and aseptic 

meningitis was present in one case.

CDC learned several lessons from the epidemiology of the mumps cases. Few infants were affected and 

minimal outbreaks were reported in schools or day care centers. The mumps cases did not spread to 

unvaccinated populations. Cases with mild clinical presentation among vaccinated persons might have 

delayed recognition of cases. Congregate settings facilitated transmission. For example, CDC’s casecontrol study in Kansas with 97 cases and 147 controls demonstrated that residence in a dormitory or 

exposure to mumps increased risk. Several questions remain unanswered about the epidemiology of the 

mumps cases. Why were females more affected? What was the reason for the outbreak starting in 

Iowa? Why were incidence rates highest in Iowa?

CDC learned several lessons from the laboratory diagnosis of the mumps cases. The performance of 

IgM tests varied. IgM responses might not occur or might be delayed. Immunoglobulin G (IgG) acute 

specimens were positive in many cases. However, efforts to obtain two IgG specimens were difficult, 

particularly during the outbreak. Real-time PCR had a low yield and was higher when specimens were 

taken early in the course of disease.

For example, CDC’s study in Kansas with 32 students with mumps detected only nine positive results. 

Real-time PCR samples were positive in 8 out of 9 specimens taken during the first three days following 

the onset of symptoms. Preliminary data from Iowa showed similar results. The ability to rule out cases 

on the basis of negative laboratory results was difficult. Several questions remain unanswered about the 

laboratory diagnosis of the mumps cases. What are the kinetics of serologic response among vaccinated 

persons? What are the true correlates of immunity for mumps? Is there a protective IgG level of antibody 

titers?

CDC learned several lessons from surveillance of the mumps cases. The existing surveillance system 

was not adequate for the mumps outbreak. The current case report form was not sufficient to report the 

absence of parotitis or asymptomatic cases. The clinical case definition of mumps varied among states. 

Several questions remain unanswered about surveillance of the mumps cases. Was mumps virus 

circulating endemically? Were mild symptomatic cases not detected by the surveillance system before 

the outbreak? Were cases in vaccinated persons ruled out by negative laboratory tests? Were mild 

symptomatic cases over-diagnosed during the outbreak due to enhanced surveillance?

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CDC learned several lessons from vaccine effectiveness of the mumps cases. Efforts to study vaccine 

effectiveness in settings with high two-dose vaccine coverage were difficult. For example, CDC 

conducted a study to determine attack rates in two highly affected college campuses in Iowa with a case 

definition of parotitis, orchitis, culture or submand/mental swelling. The study showed a 2% attack rate in 

colleges where 97% of students had received two vaccine doses and a 3.8% attack rate in colleges 

where 77% of students had received two vaccine doses. Attack rates in students who lived in dormitories 

were approximately twice those in students who did not live in dormitories.

Efforts to measure vaccine performance were challenging. For example, the Iowa college study showed 

a vaccine failure rate among two-dose recipients of ~8% with a broad case definition and ~3% with a 

restricted definition of “parotitis or orchitis lasting >2 days.” However, the attack rates of 2%-4% in Iowa 

were lower compared to previous outbreaks with attack rates of 2%-18% and 25%-49%. Several 

questions remain unanswered about vaccine effectiveness of the mumps cases. Could mumps 

outbreaks be prevented in the future with the current MMR vaccine? Could the current MMR vaccine 

eliminate mumps? Could a third dose of MMR be used for outbreak prevention?

CDC learned several lessons from waning immunity of the mumps cases. Preliminary data did not 

appear to show that waning immunity played an important role. For example, CDC’s study in Nebraska 

with 450 students who had received two MMR doses demonstrated that 7% were seronegative based on 

IgG testing. CDC’s cross-neutralization studies with FDA did not show evidence of genetic drift or 

mutations giving rise to vaccine escape. Several questions remain unanswered about waning immunity 

of the mumps cases. Is IgG a solid correlate of immunity? What are the protective levels of immunity? 

What is the role of cell-mediated immunity?

CDC learned several lessons from outbreak control of the mumps cases. Intervention strategies were 

limited to settings of high two-dose coverage. Guidance was provided on isolation. For example, CDC’s 

study in Kansas with 32 students showed that viral shedding appeared to be unlikely after three days 

following the onset of symptoms. In another study in Kansas with 134 students who were advised to be 

isolated, 100 adhered to the recommendation. Compliance was higher among students told to be isolated 

< 4 days. Two key questions remain unanswered about outbreak control of the mumps cases. Is 

isolation useful for mumps control? Do dormitories enhance transmission?

Although a number of questions remain unanswered, CDC identified several potential reasons the 

mumps outbreak occurred. The importation of cases was unrecognized. Recognition of the outbreak 

was delayed due to unfamiliarity among physicians of clinical illness and vaccine modified disease. 

Some early cases may have been ruled out with negative IgM results. College settings played a major 

role in transmission, primarily because of lower two-dose vaccine coverage compared to other school 

settings, poor adherence to isolation guidance, and difficulties in truly isolating students in dormitory 

settings.

Vaccine effectiveness of ~90%-95% and two vaccine doses might have resulted in the accumulation of 

susceptible persons sufficient to sustain transmission and maintain a sizeable outbreak on a periodic 

basis. The contribution of waning immunity is still unknown at this time. However, high MMR vaccine 

coverage levels and vaccine effectiveness mostly likely prevented thousands of additional mumps cases. 

Incidence of the 2006 mumps outbreak was relatively low compared to previous outbreaks. The disease 

appeared to be modified with lower rates of complications and hospitalizations.

Dr. Dayan confirmed that several actions would be taken in the future based on lessons learned from the 

mumps outbreak and current unanswered questions. Surveillance would be improved. Better case 

definitions and case report forms would be developed. Laboratory diagnosis would be strengthened to 

understand the kinetics of immune response, including cell-mediated immunity. The development of new 

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ACIP Meeting Minutes October 25-26, 2006 Page 52

laboratory tests would be considered. Adequate guidelines for isolation in colleges would be created. 

The effectiveness of current vaccines and policy would be reviewed.

Dr. Wallace reported that the most recent problems in the vaccine supply were due to influenza, tetanuscontaining vaccines, MMR and varicella vaccines, Prevnar conjugate vaccine (PCV) I and II, Menactra®, 

outbreak responses, and adolescent, adult and niche vaccines. The most significant issues for influenza 

during the 2000-2001 to 2006-2007 seasons included production delays, greater supply than demand, 

late season demand, shortages, manufacturer uncertainties, and later than desired production and 

distribution.

Several approaches were taken to address problems with influenza vaccine, such as prioritizing high-risk 

populations; implementing a tiering strategy; producing less vaccine the following year; producing vaccine 

late in the season; prioritizing, redistributing and extending the vaccination season; planning for 

contingencies; and promoting use of the available supply. Several manufacturers are making significant 

investments to expand capacity of influenza vaccine production.

The vaccine supply was also challenged for routine vaccination with the tetanus and diphtheria/tetanus 

toxoid, DTaP, MMR, varicella, PCV I and II, and MCV4 vaccines. These resulted from problems which 

included updated GMP requirements, updates to the manufacturing process, fill line issues, abrupt 

departure from the market by manufacturers, and high demand.

Several approaches were taken to address problems with routine vaccination, such as prioritizing tetanus 

toxoid containing vaccine for wound care; prioritizing vaccine based on provider supply; deferring certain 

doses when the supply was inadequate; delaying timing of vaccine administration; and reinforcing 

recommendations to defer vaccination to certain populations. Current problems with the vaccine supply 

include the Hib, pediatric hepatitis A (HepA), adult HepA and HepB, and Tdap vaccines.

Four major issues are the source of vaccine supply problems. The current vaccine system has minimal 

redundancy due to sole-source vaccines and mergers of manufacturers. Most vaccines are produced at 

capacity with different timetables. The existing vaccine system is complicated, dynamic and constantly 

changes. Both real and perceived risks and benefits should be addressed. Several solutions have been 

applied over the past few years to address these problems.

The National Childhood Vaccine Injury Act (NCVIA) of 1986 was enacted to address the increasing threat 

of liabilities. NCVIA resulted in the establishment of the National Vaccine Injury Compensation Program 

in 1988, the Vaccine Adverse Event Reporting System (VAERS), the National Vaccine Program Office 

(NVPO), and Vaccine Information Statements (VIS). VAERS was created to mandate reporting of certain 

adverse events following vaccination. NVPO was created to coordinate immunization activities across 

HHS agencies. Vaccine information statements were created with a requirement that information would 

be provided to vaccine recipients or their parents or legal guardians prior to certain vaccinations.

The VFC program was established by the Omnibus Budget Reconciliation Act of 1993 as an entitlement 

for eligible children to receive certain vaccines free of charge. The VFC program increases coverage and 

access to vaccines to children in need. The VFC program accounts for ~40%-43% of the entire national 

childhood vaccine use. VFC legislation requires a six-month vaccine stockpile of all routinely 

recommended vaccines to be used for supply disruptions and disease outbreaks. A strategic reserve of 

an additional annual influenza vaccine stockpile was established in 2004.

Update on the Vaccine Supply

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NVPO coordinates incentives for influenza vaccine manufacturers to ensure year-round influenza vaccine 

capacity. The incentives are targeted to accelerated vaccine development, licensing and domestic 

production of cell-culture influenza.

Overall, the current vaccine system is growing, but is still fragile with increasing complexity. Dr. Wallace 

announced that the public could review up-to-date information on shortages of routine vaccines on the 

CDC web site.

Dr. Linda Venczel, of CDC, reported that the GPEI is based on four key strategies: (1) routine 

immunization with a polio-containing vaccine in all countries; (2) supplemental immunization activities; (3) 

surveillance with >157 accredited or specialized laboratories throughout the world to monitor and 

distinguish between virus transmission patterns; and (4) mop-up activities for outbreak control and rapid 

response in limited geographical areas. The World Health Assembly (WHA) adopted the GPEI in 1998 

due to 125 polio endemic countries with >350,000 polio cases. Substantial progress has been made 

since that time based on four polio endemic countries in 2006 with 1,441 cases.

Data from June 4-October 4, 2006 showed that northern Nigeria, the Pakistan/Afghanistan border, and 

two states in northern India were the districts most infected with polio. From 2003-2006, 82% of the 

poliovirus spread was of Nigerian origin and 18% was of Indian origin. A one-year halt of vaccination 

activities in Nigeria caused poliovirus spread to other countries that had weak routine immunization 

programs. From 2005-2006, the contribution of outbreaks to overall cases dramatically shifted from 

importation of outbreaks to indigenous cases in endemic countries.

Based on the 2003-2004 outbreaks, WHA adopted new standards for polio outbreak response in May 

2006 with five components: (1) a “fast” response started within four weeks; (2) a “very large” response 

covering 2-5 million children; (3) a “high quality” response implemented house-to-house to reach all 

children; (4) a “sustained” response for a minimum of three rounds to cover missing transmission; and (5) 

use of the licensed monovalent “optimal vaccine” for poliovirus types 1 and 3.

Complete and adequate implementation of the outbreak response strategy stopped or controlled all 

outbreaks that started in 2003-2005. The strategy was successfully implemented in Namibia, Nepal and 

Yemen, but the most significant risks remain in Somalia, Ethiopia, Angola, the Democratic and Republic 

of Congo due to hard-to-reach populations, poor surveillance and breakthrough cases. 

A resurgence of cases was observed in Nigeria, India, Afghanistan and Pakistan from October 2005 to 

October 2006. Pakistan and Afghanistan accounted for 52 polio cases in 2006 due to a lack of security 

for healthcare workers and difficulties in reaching nomadic or tribal populations. However, large 

geographic areas and most densely populated areas in these countries are polio-free. 

India accounted for 416 polio cases in 2006. The outbreak represents a decline in certain areas in quality 

of campaign implementation, fatigue among healthcare workers, community members who continually 

needed to be involved or exposed to polio vaccination, and quality and non-compliance issues in 

consistently reaching children in west Uttar Pradesh. However, Bihar has worked impressively to address 

quality issues and enhance government involvement. The spread of polio from the Western Uttar 

Pradesh outbreak was limited. Strategies are being explored to combine polio vaccination with other 

activities to address community needs.

Update on the Global Polio Eradication Initiative (GPEI)

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Nigeria accounted for 920 polio cases in 2006. This outbreak was in part due to many children not 

receiving any doses of OPV (>30%). There has also been sub-optimal efforts to obtain ownership from 

local leaders. Many of the activities have revolved to ensure no additional spread into neighboring 

countries. However, southern states of Nigeria remain polio-free. International spread from Nigeria in 

2006 is limited to Niger. “Immunization Plus Days” in which polio vaccination is integrated with bed nets, 

vitamin A and other community needs appear to have reached more children than polio-only campaigns.

The Horn of Africa accounted for 48 polio cases from April-October 2006 due to porous border areas, 

refugee camps, and nomadic and hard-to-reach populations. However, synchronized campaigns were 

launched that should help to halt further spread. Activities are being coordinated with local NGOs and 

GPEI partner funding for community mobilization strategies and vaccine. Quality campaign 

implementation was improved and efforts were made to vaccinate all persons in refugee camps.

Several new strategies are being implemented under the GPEI. Data from the monovalent polio vaccine 

type 1 (mOPV1) trial that was conducted in Egypt confirmed that a single mOPV1 dose resulted in ~75% 

seroconversion compared to ~30% seroconversion with trivalent OPV. Research with a birth dose of 

mOPV1 is being conducted in India to reach young children as quickly as possible. A combination of 

mOPV1 and IPV will be piloted in India next year to evaluate logistical challenges. Data will soon be 

available from mOPV1 licensing studies that were conducted in Punjab and Andra Pradesh. A fractional 

IPV dose study will be launched in Oman in November 2006. The results will be tracked over time and 

followed up with a challenge dose of mOPV1.

A study will be piloted in a large metropolitan area in Indonesia to evaluate the switch from an OPV to IPV 

routine schedule. Many countries are implementing an integrated approach in which polio vaccination is 

combined with other activities to respond to community requests. CDC and the global laboratory network 

developed a new algorithm to obtain laboratory results twice as fast to enable rapid outbreak response. 

The algorithm can be used to obtain results in <1 week to confirm wild poliovirus cases. New 

communications initiatives were implemented with national governments, religious leaders and local 

leaders in India and Nigeria to obtain input on community needs and ensure accurate and appropriate 

information is conveyed at the local level.

Efforts are being made to protect polio-free areas from importation. Brazil and Saudi Arabia are 

implementing vaccine requirements for OPV for certain country nationals to enter their respective 

countries. Persons entering these countries must provide complete documentation of OPV vaccination. 

WHO’s International Travel and Health Regulations will be updated to recommend full polio immunization 

for all travelers to and from infected areas. Efforts are being made to incorporate a standing 

recommendation into the International Health Regulations beginning with the 2007 edition.

Overall, all outbreaks in polio-free areas since 2003 have been stopped or appropriate actions are being 

taken to reach this goal. Parts of Afghanistan, India, Nigeria and Pakistan have ongoing transmission 

that threatens the polio-free areas of these four countries and >190 additional countries in the world. The 

2007 GPEI strategic approach will focus on stopping transmission in endemic areas and addressing any 

new outbreaks that occur.

Ms. Annelise Casano-Dickerson, of CDC, described activities that were conducted to respond to U.S.-

bound East African refugees with possible exposure to poliovirus. The United States resettles 50,000-

70,000 refugees each year. The percentage of African refugees increased from 9% in 1998 to 39% in 

2005. The Immigration and Nationality Act was amended in 1996 to require vaccination of immigrants 

admitted as legal permanent residents or “green card holders.” Because this law only applies to 

immigrants, U.S.-bound refugees are not required to have any vaccination before or after arrival unless 

school entry or other U.S. requirements apply.

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Implementation of WHO vaccine recommendation is variable in refugee camps and typically depends on 

non-governmental organizations providing health care. Moreover, refugees are frequently excluded from 

national vaccination campaigns. Resettled refugee children are generally vaccinated under the VFC 

program, but vaccination of resettled adult refugees varies among states. Of 45 states that responded to 

a survey on routine polio vaccination policies for adult refugees, none would routinely vaccinate adult 

refugees from Kenya against polio due to adherence to ACIP recommendations. Refugee Medical 

Assistance funds cover state costs of providing some adult vaccinations after refugees arrive in the 

United States. Refugees are eligible to adjust their status to a legal permanent resident one year after 

arrival, but those who elect to take this action are required to be vaccinated as recommended by ACIP.

Dadaab refugee camp in Kenya includes three refugee camps with ~140,000 Somali refugees and was 

the source of the type 1 poliomyelitis case reported to CDC. U.S.-bound refugees from Dadaab and 

Kakuma refugee camps in Kenya and also from Tanzanian refugee camps spend at least three days in a 

transit center in Nairobi. Somalia had a reintroduction of polio in 2004 and ongoing transmission since 

2005 with 216 reported cases. Four polio vaccination campaigns for children <5 years of age were 

launched in Dadaab in 2006.

In October 2006, CDC was notified of the first case of polio in Kenya in 22 years. The wild poliovirus type 

1 case occurred in a female Somali refugee 3 years of age with an onset of paralysis in September 2006. 

The genetic sequence of the virus was linked to recent poliovirus isolates imported from Kismayo, 

Somalia and wild poliovirus type 1 imported from Nigeria. A joint response with national and international 

teams was initiated. From September 1-October 20, 2006, ~1,347 refugees had resettled in the United 

States, were en route from Dadaab, or were scheduled to arrive from the Nairobi transit center. An 

additional 1,000 refugees in the Dadaab camp are being considered for U.S. resettlement within the next 

two months.

CDC made the following recommendations to state and local health departments based on the 

poliomyelitis case in the Dadaab camp: (1) administer one IPV dose to resettled and en route refugees; 

(2) administer one OPV dose to refugees in the Dadaab camp; (3) obtain one stool sample from en route 

refugees; and (4) perform active surveillance once per week for four weeks of all refugees. The 

movement of refugees who were still in the Dadaab camps was temporarily halted pending an 

investigation and vaccination before departure.

An emergency regional campaign with mOPV1 is scheduled to be launched in Kenya on November 3, 

2006. The campaign will cover ~250,000 children <15 years of age and will be coordinated with Somalia 

and Ethiopia. The next vaccination round is scheduled for December 2006 and might be expanded to 

included Nairobi and other high-risk areas. A clinical and epidemiological investigation in the refugee 

camp is ongoing.

Two different perspectives were provided on the GPEI. On the one hand, Dr. Stanley Plotkin, of sanofi 

pasteur, noted that consideration should be given to refocusing GPEI resources to address other needs in 

endemic areas. For example, the GPEI has resulted in an investment of >$4 billion to date, but was 

scheduled to end in 2000. Moreover, eradication of polio is an extremely complex problem. On the other 

hand, Dr. Hull pointed out that the GPEI should be continued due to its contributions to several non-polio 

areas. For example, the GPEI served as the foundation for the dramatic decline in measles in Africa, 

worldwide introduction of vitamin A supplementation, and elimination of rubella and measles in the United 

States.

In response to both comments, Dr. Venczel agreed that countries must be realistic about the challenges 

in eradicating polio. However, her position was that this goal could be achieved. She emphasized that a 

resurgence of polio cases would most likely occur if routine polio immunization and other GPEI activities 

were discontinued.

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CDC/NCIRP [proposed]. Dr. Anne Schuchat reported that after the June 2006 ACIP meeting, CDC 

published an update in the MMWR on routine vaccination coverage in children 19-35 months of age with 

the 4:3:1:3:3:1 series. Racial disparities were eliminated in the series. Prevnar coverage in this age 

group dramatically increased from the 2004 period. Substantial variability among states continued. The 

newest vaccines still need to be improved. CDC also published updates in the MMWR on influenza 

vaccine coverage in young children and for school entry.

FDA. Dr. Norman Baylor reported that FDA approved the ID Biomedical influenza vaccine. FDA will 

continue to collaborate with manufacturers to facilitate involvement of even more influenza vaccine 

manufacturers and also to develop pandemic vaccine.

HRSA. Dr. Indira Jevaji reported that the extensive discovery process in phase 1 of the Omnibus Autism 

Proceeding is coming to an end. The deadline for submission of expert reports by petitioners is February 

16, 2007. One of the Special Masters assigned to the case will determine causality between the MMR 

vaccine or thimerosal-containing vaccines. The court will apply the determination to individual cases after 

the hearing. To date, ~4,700 thimerosal cases have been filed under the National Vaccine Injury 

Compensation Program (VICP).

Several bills were introduced in the current Congressional session. The House passed a bill in July 2006 

that would add an excise tax to meninogococcal and HPV vaccines, but the Senate has not passed 

similar legislation. Two requirements must be met to add vaccines to VICP. First, the vaccine must be 

evidence-based, recommended by CDC for routine immunization of children and published in the MMWR. 

Second, Congress must pass an excise tax.

VICP coverage begins on the effective date the excise tax was enacted. Petitioners have a two-year 

window to file a claim for injuries that occurred up to eight years before the effective date of coverage for 

the newly added vaccine. VICP currently covers 14 vaccines that represent ~95% of vaccines distributed 

in the United States.

NVPO. Dr. Angela Shannon reported that NVPO is the lead office for ~10 of 199 tasks in the HHS 

implementation plan for the National Strategy for Pandemic Influenza. NVPO’s responsibilities include 

vaccine production capacity, prioritization of vaccine, antiviral drugs and other countermeasures, and 

communication of research activities.

NVPO is the co-lead for the establishment of a new HHS-wide influenza risk management group that will 

provide a senior-level forum to (1) identify and assess risk management issues related to the 

development, acquisition, deployment and utilization of medical and public health countermeasures for 

pandemic and seasonal influenza; (2) monitor program milestones and timelines; (3) decide 

responsibilities for addressing issues; (4) track and follow-up activities for assigned tasks; and (5) 

facilitate interagency coordination and decision-making on key cross-cutting issues.

NVPO developed and submitted two documents to the HHS Secretary: “Ensuring the Optimal Safety of 

Vaccines” report and “The National Vaccine Safety Plan Priority Goals and Objectives” vaccine safety 

strategic plan. Both documents are undergoing the final review process at HHS. NVPO’s FY’07 unmet 

needs and priorities include the vaccine supply and financial support for vaccine economic studies. 

NVPO is interested in receiving proposals for its FY’07 priorities to optimize funding. NVAC, its four 

standing subcommittees and two workgroups met in September 2006. The public can access the NVPO 

Ex- Officio Reports

This document has been archived for historical purposes.
ACIP Meeting Minutes October 25-26, 2006 Page 57

web site to review slides and summaries of the meetings. The next NVAC meeting will be held on 

February 6-7, 2007.

Ms. Lyn Redwood, of SafeMinds, applauded CDC’s efforts to investigate vaccine safety issues. 

However, she pointed out that this effort was undertaken only because CDC was reprimanded in the 

2005 IOM report on vaccine safety research, public access and public trust. She expressed strong 

concerns about CDC’s ability to conduct vaccine safety investigations due to its inherent ideological and 

financial conflicts of interest. Most notably, a recent investigative report revealed CDC’s close ties to 

vaccine manufacturers. As a result, an independent entity with no inherent conflicts would be needed to 

oversee vaccine safety monitoring. Ms. Redwood advised CDC to recuse itself from vaccine safety 

monitoring and support the establishment of an independent entity.

Dr. Abramson thanked the participants for attending the meeting. With no further discussion or business 

brought before ACIP, Dr. Abramson adjourned the meeting at 3:08 p.m. on October 26, 2006.

 I hereby certify that to the best of my knowledge, 

the foregoing Minutes of the October 25-26, 

2006 ACIP Meeting are accurate and complete.

___________________ ______________________________________

Date Jon S. Abramson, M.D., Chair,

Advisory Committee on Immunization Practices

Public Comment Period

Closing Session

This document has been archived for historical purposes.