This book was produced by the Communication and Education Branch, National Center for Immunization and 

Respiratory Diseases, Centers for Disease Control and Prevention. It was printed and distributed by the Public 

Health Foundation. For additional copies, contact the Public Health Foundation at 877-252-1200 or website http://

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The most current, 508-compliant version of this book is available at CDC’s Pink Book website: https://www.cdc.gov/

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E-mail address for comments, questions, or suggestions about the contents of this book: nipinfo@cdc.gov.

14TH EDITION

Edited by:

Elisha Hall, PhD, RD

A. Patricia Wodi, MD

Jennifer Hamborsky, MPH, MCHES®

Valerie Morelli

Sarah Schillie, MD, MPH, MBA

Layout and Design by:

Peggy Dana 

U.S.Department of 

Health and Human Services

Centers for Disease

Control and Prevention

EPIDEMIOLOGY

AND PREVENTION OF

VACCINE-PREVENTABLE 

DISEASES

https://www.cdc.gov/vaccines/pubs/pinkbook/front-matter.html Aug 2021
Milestones in the History of Vaccination

The findings and conclusions in this book are those of the author(s) and do not necessarily represent the 

views of the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for 

identification only and does not imply endorsement by the Public Health Service or the U.S. Department 

of Health and Human Services. References to non-CDC sites on the Internet are provided as a service to 

readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the 

U.S. Department of Health and Human Services. CDC is not responsible for the content of these sites. URL 

addresses were current as of the date of publication.

The editors would like to thank Skip Wolfe, who thoughtfully conceived, executed, and managed the Pink 

Book appendices.

The editors would also like to thank Dr. Kathy Towers-Solis for supporting the Pink Book through each new 

edition and promoting its importance for the public health workforce providing immunizations.

Finally, the editors would like to thank Dr. William L. Atkinson, who summarized, standardized, and compiled 

CDC’s vaccine-preventable disease and vaccine teaching materials to create the Pink Book.

“He just thought it up and did it.” – Apocalypse Now

This illustration depicts Bordetella pertussis.

Graphic from the Public Health Image Library.

Suggested Citation:

Centers for Disease Control and Prevention. Epidemiology and Prevention 

of Vaccine-Preventable Diseases. Hall E., Wodi A.P., Hamborsky J., et al., eds. 14th ed. 

Washington, D.C. Public Health Foundation, 2021.

On the cover

400BCE

Hippocrates describes 

diphtheria, epidemic jaundice, 

and other conditions

1100s

Variolation for smallpox first 

reported in China

1721

Variolation introduced 

into Great Britain

1796

Edward Jenner inoculates 

James Phipps with cowpox, and 

calls the procedure vaccination 

("vacca" is Latin for cow)

ii

Table of Contents
Milestones in the History of Vaccination

1 Principles of Vaccination 

Immunology and Vaccine-Preventable Diseases. 

Types of Immunity. 

Classification of Vaccines. 

Selected References. 

2 General Best Practice Guidance for Immunization

Timing and Spacing of Vaccines. 

Doses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Adverse Reactions Following Vaccination. .

Contraindications and Precautions to Vaccination. .

Selected References. .

3 Immunization Strategies for Healthcare Practices 

and Providers 

Standards for Child, Adolescent, and Adult 

Immunization Practices. . 

The Guide to Community Preventive Services. .

Health Care Practice Quality Improvement Programs. .

Essential Strategies for Health Care Practices. .

System-Based Barriers. .

Creating a Culture of Immunization within a Practice. .

Selected References. .

4 Vaccine Safety 

Adverse Events Following Immunization and Assessment 

of Causality. .

Importance of Vaccine Safety Programs. .

Assessing and Monitoring Vaccine Safety. .

The Vaccination Provider’s Role in Vaccine Safety. .

Selected References. .

5 Storage and Handling

Vaccine Cold Chain. .

Vaccine Storage and Handling Standard Operating 

Procedures (SOPs). .

Vaccine Storage and Temperature Monitoring Equipment. .

Organizing and Storing Vaccine in Storage Unit. .

Temperature Ranges. .

Vaccine Inventory Management. .

Vaccine Transport. .

Selected References. .

1870

Louis Pasteur creates the 

first live, attenuated bacterial 

vaccine (chicken cholera)

1884-85

Pasteur creates the first 

live, attenuated viral vaccine 

for use in humans

1900

Paul Ehrlich formulates 

receptor theory of immunity

1901

First Nobel Prize in Medicine 

to von Behring for 

diphtheria antitoxin

1909 

Theobald Smith discovers a 

method for inactivating 

diphtheria toxin

Table of Contents

iii
Milestones in the History of Vaccination

6 Vaccine Administration 

Staff Training and Education. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Before Administering Vaccine. .

Vaccine Administration. .

Patient Care after Vaccine Administration. .

Selected References. .

7 Diphtheria 

Corynebacterium diphtheriae. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Diphtheria Toxoid-containing Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Diphtheria Disease. .

Selected References. .

8 Haemophilus influenzae

Haemophilus influenzae. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Haemophilus influenzae type b Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Hib Disease. .

Selected References. .

1919

Calmette and Guerin create BCG, 

the first live attenuated 

bacterial vaccine for humans

1923

First whole-cell pertussis 

vaccine tested

Gaston Ramon develops 

diphtheria toxoid

1926

Ramon and Christian Zoeller 

develop tetanus toxoid

1931

Goodpasture describes 

a technique for viral 

culture in hens’ eggs

1936

Thomas Francis and 

Thomas Magill develop 

the first inactivated 

influenza vaccine

iv

Table of Contents
Milestones in the History of Vaccination

9 Hepatitis A 

Hepatitis A Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Hepatitis A Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting for Hepatitis A. .

Selected References. .

10 Hepatitis B

Hepatitis B Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Hepatitis B Prevention Strategies. .

Hepatitis B Vaccine. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Hepatitis B. .

Selected References. .

11 Human Papillomavirus 

Human Papillomaviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United Statess. .

Prevention. .

Human Papillomavirus Vaccine. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of HPV Infection. .

Selected References. .

1948

John Enders and colleagues 

isolate Lansing Type II 

poliovirus in human cell line

1954

Enders and Peebles 

isolate measles virus 

Francis Field Trial of inactivated 

polio vaccine

1955

Inactivated polio 

vaccine licensed

1961

Human diploid 

cell line developed

1963

Measles vaccine licensed

Trivalent oral polio 

vaccine licensed

Table of Contents

v
Milestones in the History of Vaccination

1965

Bifurcated needle for 

smallpox vaccine licensed

1966

World Health Assembly 

calls for global smallpox 

eradication

12 Influenza 

Influenza Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Influenza Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Influenza. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

Selected References. .

13 Measles

Measles Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Measles Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting for Measles. .

Selected References. .

14 Meningococcal Disease

Neisseria meningitidis. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Meningococcal Vaccines. .

Vaccination Schedule And Use. .

Immunogenicity and Vaccine Effectiveness. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Meningococcal Disease. .

Selected References. .

1967

Maurice Hilleman develops 

Jeryl Lynn strain of 

mumps virus

1969

Stanley Plotkin develops 

RA 27/3 strain of rubella 

vaccine virus

1971

MMR vaccine licensed

vi

Table of Contents
Milestones in the History of Vaccination

15 Mumps

Mumps Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Mumps Vaccine. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting for Mumps. .

Selected References. .

16 Pertussis

Bordetella pertussis. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Pertussis-containing Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Pertussis. .

Selected References. .

1977

Last indigenous case 

of smallpox 

(Somalia)

1979

Last wild poliovirus 

transmission in the U.S.

1981

First hepatitis B 

vaccine licensed

1983

Smallpox vaccine withdrawn 

from civilian market

1986

First recombinant vaccine

licensed (hepatitis B) 

National Childhood 

Vaccine Injury Act passed

Table of Contents

vii
Milestones in the History of Vaccination

1989

Two-dose measles vaccine 

recommendation

1990

First polysaccharide conjugate 

vaccine licensed 

(Haemophilus influenzae type b)

17 Pneumococcal Disease

Streptococcus pneumoniae. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Pneumococcal Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Pneumococcal Disease. . . . . . . . . . . . . . . . . . . . . 271

Selected References. .

18 Poliomyelitis 

Poliovirus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Poliovirus Vaccines. .

Vaccination Schedule and Use. .

Contraindications And Precautions To Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Poliomyelitis. .

Selected References. .

19 Rotavirus

Rotavirus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Rotavirus Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Rotavirus. .

Selected References. .

1994

Polio elimination certified 

in the Americas 

Vaccines for Children 

program begins

1995

Varicella vaccine licensed

Hepatitis A vaccine licensed

First harmonized childhood 

immunization schedule published

1996

Acellular pertussis vaccine 

licensed for infants

viii

Table of Contents
Milestones in the History of Vaccination

20 Rubella

Rubella Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Rubella Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting for Rubella. .

Selected References. .

21 Tetanus

Clostridium tetani. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Tetanus Toxoid-containing Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Tetanus. .

Selected References. .

1997

Sequential polio vaccination 

recommended

1998

First rotavirus 

vaccine licensed

1999

Exclusive use of inactivated 

polio vaccine recommended

Rotavirus vaccine withdrawn

2000

Pneumococcal 

conjugate vaccine 

licensed for infants

2003

Live attenuated influenza 

vaccine licensed

Table of Contents

ix
Milestones in the History of Vaccination

2004

Inactivated influenza 

vaccine recommended for all 

children 6–23 months of age

2005

MMR-varicella (MMRV) licensed

22 Varicella

Varicella Zoster Virus. .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Varicella Vaccines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Varicella. .

Selected References. .

23 Zoster

Varicella-Zoster Virus (VZV). .

Pathogenesis. .

Clinical Features. .

Epidemiology. .

Secular Trends in the United States. .

Zoster Vaccines. .

Vaccination Schedule and Use. .

Contraindications and Precautions to Vaccination. .

Vaccine Safety. .

Vaccine Storage and Handling. .

Surveillance and Reporting of Zoster. .

Selected References. .

2004

Indigenous transmission of 

rubella virus interrupted

2005

Acellular pertussis vaccines licensed 

for adolescents 

and adults

2006

Second generation rotavirus 

vaccine licensed

x

Table of Contents
Milestones in the History of Vaccination Milestones in the History of Vaccination

Appendix A: Schedules and Recommendations...............................................................A–1

Catch-up Schedule Job Aids for Persons Aged 0 Through 18 Years. . 

Diphtheria-, Tetanus-, and Pertussis-Containing Vaccines Catch-Up Guidance 

for Children 4 Months through 6 Years of Age ......... .............. . .............. . . .............. . . ...........A–3

Hib vaccine products: ActHIB, Pentacel, Hiberix, or unknown ...... ............... . . ............. . . . . .A–5

Hib vaccine products: PedvaxHIB vaccine only ....... ............. . . .............. . . .............. . . ............A–8

Inactivated Polio Vaccine (IPV).............. . . . .............. . . .............. . . ............. . ............... . . ........... .A–10

Pneumococcal Conjugate Vaccine (PCV) Catch-Up Guidance for Children

4 Months through 4 Years of Age . . . .............. . . . .............. . . ............. . . .............. . . . .............. . . . . .A–12

Tetanus-, Diphtheria-, and Pertussis-Containing Vaccines Catch-Up Guidance

for Children 7 through 9 Years of Age ........ . . .............. . . . ............. . . .............. . . .............. . ...... .A–15

Tetanus-, Diphtheria-, and Pertussis-Containing Vaccines Catch-Up Guidance

for Children 10 through 18 Years of Age .......... . . .............. . . ............. . . . ............. . . . .............. .A–17

Healthcare Personnel Vaccination Recommendations ......... . . ............. . . .............. . . ......... .A–19

Recommended and Minimum Age and Intervals Between Doses 

of Routinely Recommended Vaccines. . 

Recommended Intervals between Administration of Antibody-containing 

Products and Measles- or Varicella-containing Vaccine. . 

Vaccination of Persons with Primary and Secondary Immune Deficiencies. . 

Contraindications and Precautions to Commonly Used Vaccines. . 

Additional Resources for Schedules and Recommendations. . 

Appendix B: Vaccines....................................................................................................................................................B–1

United States Vaccines. .

Vaccine Excipient Summary. .

Latex in Vaccine Packaging. . 

Vaccine-Preventable Disease Terms in Multiple Languages. . 

Resources for Vaccines. . 

2006

First human papillomavirus 

vaccine licensed

2006

First herpes zoster 

vaccined licensed

2009

H1N1 influenza 

pandemic declared

2010

Influenza vaccine 

recommended for all persons 6 

months and older

2013

First quadrivalent influenza 

vaccine licensed

Appendices

xi
Milestones in the History of Vaccination

Appendix C: Vaccine Information Statements...................................................................C–1

You Must Provide Patients with Vaccine information Statements – It’s Federal Law!. .

Instructions for the Use of Vaccine Information Statements. .

Vaccine Information Statements: Frequently Asked Questions. .

Additional Resources for Vaccine Information Statements. . 

Appendix D: Vaccine Safety...............................................................................................................................D–1

Vaccine Adverse Event Reporting System (VAERS). .

Vaccine Administration: Preventing Vaccine Administration Errors. .

Vaccine Injury Compensation Program (VICP). . .

Countermeasures Injury Compensation Program (CICP). . .

Additional Resources for Vaccine Safety. . .

2014

First serogroup B 

meningococcal 

vaccine licensed

2014

First 9-valent recombinant 

protein subunit

HPV vaccine licensed

2017

First recombinant zoster 

vaccine licensed

2-dose HepB vaccine using 

a novel adjuvant licensed

2020

World Health Organization 

declares COVID-19 pandemic

2020

FDA authorizes the first 

COVID-19 vaccine through 

Emergency Use Authorization

Note: Appendices are periodically updated. For the most recent versions, refer to the appendices 

found online at: https://www.cdc.gov/vaccines/pubs/pinkbook/appendix/index.html

xii

Appendices