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Hepatitis A and B Vaccines

Hepatitis A Vaccine

Long-term protection from hepatitis A virus (HAV) infection can be achieved through active, preexposure vaccination with hepatitis A vaccine. Inactivated hepatitis A vaccines licensed for use in the United States are Havrix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), VAQTA® (Merck & Co., Inc., Whitehouse Station, New Jersey), and Twinrix® (GlaxoSmithKline Biologicals), a combined hepatitis A and hepatitis B vaccine (1,2). All are produced from HAV grown in cell culture, inactivated with formalin, and formulated with alum adjuvant in pediatric and adult dosages that are 94%--100% effective in preventing clinical disease among juveniles and adults when administered according to recommended schedules (1,2) (Table 3).

Protective levels of antibody to HAV (anti-HAV) develop among 94%--100% of vaccinated persons within 1 month after administration of the first dose. A second dose results in protective levels of antibody among all persons vaccinated, and is considered necessary for long-term protection. Estimates of antibody persistence suggest protective levels of anti-HAV persist for >20 years (1).

A delay in administration of the second vaccine dose does not result in lowered final antibody levels or seroconversion rates, and restarting the vaccine series if the second dose is delayed is not needed. Vaccination begun with vaccine from one manufacturer can be completed with vaccine from the other (3,4). Hepatitis A vaccine can be administered at the same time as other vaccines, including hepatitis B vaccine, without affecting immunogenicity or increasing the frequency of adverse events.

Adverse Reactions

The most frequently reported adverse reactions occurring <3 days after vaccination are soreness at the injection site (53%--56%), headache (14--16%), and malaise (7%). Reviews of data from multiple sources have not identified any serious adverse events among juveniles or adults associated with hepatitis A vaccination (1). Any adverse event occurring after hepatitis A vaccination should be reported to the Vaccine Adverse Events Reporting System (VAERS). Reporting forms can be obtained by calling 1-800-822-7967.


Hepatitis A vaccine should not be administered to persons with a history of hypersensitivity reactions to alum, or for Havrix or Twinrix, to the preservative 2-phenoxyethanol. The safety of hepatitis A vaccination during pregnancy has not been determined. However, because this is an inactivated vaccine, the theoretical risk to the developing fetus is low. The risk associated with vaccination should be weighed against the risk for hepatitis A among women who might be at high risk for exposure to HAV infection. No special precautions are needed when vaccinating immunocompromised persons.

Serologic Testing for HAV Infection

Antibody produced after HAV infection results in lifelong immunity. Among adult populations with high rates of prior HAV infection, prevaccination testing can reduce costs by avoiding the vaccination of persons with prior immunity. However, the vaccination of an immune person does not increase the risk for adverse events. The decision to test should be based on 1) expected prevalence of immunity; 2) cost of vaccination compared with cost of serologic testing; and 3) likelihood that testing will not interfere with initiating vaccination.

Prevaccination testing of younger juveniles (ages <15 years) is not indicated because of their low prevalence of infection. Prevaccination testing is most likely to be cost-effective for older juveniles and adults born in countries, or who have been residents for extensive periods in countries, with a high endemicity of HAV infection (e.g., Mexico, South and Central America, Africa, and all of Asia except Japan), populations with historically high rates of infection (e.g., American Indians or Alaska Natives), and those engaging in behaviors that place them at high risk for infection (e.g., drug users or men who have sex with men). Because anti-HAV prevalence increases with age, prevaccination testing of any person aged >40 years would likely be cost-effective (1). Commercially available tests for total anti-HAV can be used for prevaccination testing. Postvaccination testing is not indicated because of high rates of vaccine response among both adults and juveniles. In addition, no Food and Drug Administration (FDA)-approved testing method exists that has the sensitivity to detect low anti-HAV concentrations after vaccination.

Hepatitis B Vaccine

Vaccines available in the United States use hepatitis B surface antigen (HBsAg) produced in yeast cells by recombinant deoxyribonucleic acid (DNA) technology, and are formulated to contain 5--40 µg HBsAg protein/mL and 0.5 mg/mL aluminum hydroxide as the adjuvant. The two available single antigen hepatitis B vaccines are Recombivax HB® (Merck & Co., Inc., Whitehouse Station, New Jersey) and Engerix-B® (GlaxoSmithKline Biologicals, Rixensart, Belgium) (5). A combination hepatitis A and hepatitis B vaccine, Twinrix, is also licensed for persons aged >18 years old (2) (Table 4).

Antibody Response to Vaccination

Licensed formulations for both vaccines produce high (>95%) rates of protective antibody (anti-HBs >10 mIU/mL) when the complete series is administered in different schedules to infants, juveniles, and adults aged <40 years (5). Among healthy adults, 30%--50% develop a protective antibody response after the first vaccine dose, 75% after the second dose, and >95% after the third dose (5--9). Increasing the interval between the first and second dose of vaccine has little effect on immunogenicity or final antibody titer, although data are limited regarding intervals >2 months among adults (5,8). The third dose confers the maximum rate of seroprotection; it primarily acts as a booster and confers optimal long-term protection through the induction of maximum immune memory (5,9). Both licensed vaccines administered on a 0-, 1-, and 6-month schedule produce a >95% final seroprotection rate among adolescents and healthy young adults, and studies indicate that vaccination of adolescents and adults on a 0-, 2-, and 4-month, and adolescents on a 0-,12-, and 24-month schedule, achieved final seroprotection rates similar to the 0-, 1-, and 6-month schedule (8--10). In addition, a 2-dose vaccination series using Recombivax HB® at the adult dosage has been demonstrated among adolescents aged 11--15 years to produce protective antibody responses equivalent to that of the 3-dose series, although the long-term protection afforded from this schedule is not known (8,11).

The duration of vaccine-induced antibody and protection from hepatitis B virus (HBV) infection has been evaluated among vaccinated infants, juveniles, and adults (5,12--14). Studies indicate that although loss of detectable anti-HBs has ranged from 13% to 60% by 9--15 years after vaccination, immune memory provides protection from HBV infection, and protection remains intact for >15 years, the longest period for which follow-up data are available (5,12--14). Because of the long duration of protection afforded by the 3-dose vaccine series, booster doses of vaccine are not needed among vaccinated immunocompetent juveniles or adults.

Adverse Reactions

Adverse reactions associated with hepatitis B vaccine include pain at the injection site (3%--29%) and a temperature >37.7ºC (1%--6%), although these effects are reported no more frequently among vaccine recipients than among placebo recipients in controlled trials (5). Anaphylaxis has been reported in 1/600,000 vaccine recipients; however, no deaths have been attributed to vaccination. A number of case reports and case series have claimed an association between hepatitis B vaccination and serious adverse health events (e.g., multiple sclerosis) (15,16); however, these have not been proven by other epidemiologic studies (17--22). Adverse events suspected to be associated with hepatitis B vaccination should be reported to VAERS, and reporting forms can be obtained by calling 1-800-822-7967.


  1. CDC. Prevention of hepatitis A through active or passive immunization---recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48 (RR-12):1--37.
  2. CDC. Notice to readers: FDA approval for a combined hepatitis A and hepatitis B vaccine. MMWR 2001;50:806--7.
  3. Bryan JP, Henry CH, Hoffman AG, et al. Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. Vaccine 2001;19:743--50.
  4. Connor BA, Phair J, Sack D, et al. Randomized, double-blind study in health adults to assess the boosting effect of Vaqta or Havrix after a single dose of Havrix. Clin Infect Dis 2001;32:396--401.
  5. CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination---recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40 (RR-13):1--25.
  6. Davidson M, Krugman S. Recombinant yeast hepatitis B vaccine compared with plasma-derived vaccine: immunogenicity and effect of a booster dose. J Infect 1986;13(suppl A):31--8.
  7. Jilg W, Deinhardt F. Results of immunisation with a recombinant yeast-derived hepatitis B vaccine. J Infect 1986;13(suppl A):47--51.
  8. Cassidy WM, Watson B, Ioli VA, Williams, K, Bird S, West, DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001;107:626--31.
  9. Middleman AB, Kozinetz CA, Robertson LM, DuRant RH, Emans SJ. The effect of late doses on the achievement of seroprotection and antibody titer levels with hepatitis B immunization among adolescents. Pediatrics 2001;107:1065--9.
  10. Marsano LS, Greenberg RN, Kirkpatrick RB, et al. Comparison of a rapid hepatitis B immunization schedule to the standard schedule for adults. Am J Gastroenterol 1996;91:111--5.
  11. CDC. Notice to readers: alternate two-dose hepatitis B vaccination schedule for adolescents aged 11--15 years. MMWR 2000;49:261.
  12. Mahoney FJ, Stewart K, Hu H, Coleman P, Alter MJ. Progress toward the elimination of hepatitis B virus transmission among health care workers in the United States. Arch Intern Med 1997;157:2601--5.
  13. West DJ, Calandra GB. Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination. Vaccine 1996;14:1019--27.
  14. Yuen MF, Lim WL, Cheng CC, Lam SK, Lai, CL. Twelve-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine versus plasma-derived vaccine without booster doses in children. Hepatology 1999;29:924--7.
  15. Herroelen L, de Keyser J, Ebinger G. Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine. Lancet 1991;338:1174--5.
  16. Kaplanski G, Retornaz F, Durand J, Soubeyrand J. Central nervous system demyelination after vaccination against hepatitis B and HLA haplotype [Letter]. J Neurol Neurosurg Psychiatry 1995;58:758--9.
  17. Expanded programme on immunization (EPI): lack of evidence that hepatitis B vaccine causes multiple sclerosis. Wkly Epidemiol Rec 1997;72:149--52.
  18. Sadovnick AD, Scheifele DW. School-based hepatitis B vaccination programme and adolescent multiple sclerosis. Lancet 2000;355:549--50.
  19. Ascherio A, Zhang SM, Hernan MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344:327--32.
  20. Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. N Engl J Med 2001;344: 319--26.
  21. MacIntyre CR. Hepatitis B vaccine: risks and benefits of universal neonatal vaccination. J Paediatr Child Health 2001;37:215--7.
  22. Stratton K, Almario D, McCormick MC. Immunization safety review: hepatitis B vaccine and demyelinating neurological disorders. Washington, D.C.: The National Academies Press, 2002.

External Consultants: Katie Arnold, M.D., Georgia Department of Human Resources, Atlanta, Georgia; Jack Beck, Legal Aid Society of New York, New York, New York; Ellen Bentz, National Minority Aids Council, Washington, D.C.; David Bergmire-Sweat, M.P.H., American Social Health Association, Research Triangle Park, North Carolina; Joseph Bick, M.D., California Medical Facility, Vacaville, California; Kitty Bradley, Hepatitis Foundation International, Cedar Grove, New Jersey; Marie Bresnahan, M.P.H., American Liver Foundation, New York, New York; Judy Byrnes, Georgia Department of Human Resources, Atlanta, Georgia; William Cassidy, M.D., Louisiana State University Health Science Center, Baton Rouge, Louisiana; Grace Chao, M.D., University of Texas Medical Branch, Galveston, Texas; Robert L. Cohen, M.D., New York, New York; Thomas Conklin, M.D., Hampden County Correctional Center, Ludlow, Massachusetts; Anne S. DeGroot, M.D., Brown University School of Medicine, Providence, Rhode Island; Carmen C. Deseda, M.D., Puerto Rico Department of Health, San Juan, Puerto Rico; David Doolen, National Minority AIDS Council, Washington, D.C.; Ronald Feinstein, M.D., The Society for Adolescent Medicine, Birmingham, Alabama; Felicia Fong, Minnesota Department of Health, Minneapolis, Minnesota; Peter M. Ford, M.D., Queen's University, Ontario, Canada; Alan Franciscus, Hepatitis C Support Project, San Francisco, California; Joe Goldenson, M.D., Jail Health Services, San Francisco, California; Brenda Goldhammer, M.P.H., California STD/HIV Prevention Training Center, Berkeley, California; Betty Gondles, Ph.D., American Correctional Association, Arlington, Virginia; James A. Gondles, Jr., American Correctional Association, Lanham, Maryland; Betty Adams Greene, J.D., Lanham, Maryland; Robert B. Greifinger, M.D., The Bromeen Group, Dobbs Ferry, New York; Ted Hammet, Ph.D., Abt Associates, Cambridge, Massachusetts; Edward Harrison, National Commission on Correctional Health Care, Chicago, Illinois; Alicia Herman, Association of State and Territorial Health Officials, Washington, D.C.; Evalyn Horowitz, M.D., California Department of Corrections, Elk Grove, California; Judy Hubbard, Cobb County Board of Health, Atlanta, Georgia; Bert Hurowitz, Florida Department of Corrections, Tallahassee, Florida; Bethanne Jenks, M.D., Atlanta, Georgia; Glenn Johnson, M.D., Wackenhut Correctional Corporation, Austin, Texas; Renee Kanan, M.D., Correct Care Management, Seattle, Washington; Mike Kelley, M.D., Texas Department of Corrections, Huntsville, Texas; Steve Koester, Ph.D., University of Colorado at Denver, Denver, Colorado; Ronald Koretz, M.D., UCLA Medical School, Los Angeles, California; Madie LaMarre, Georgia Department of Corrections, Atlanta, Georgia; Daryl Lau, M.D., University of Texas Medical Branch, Galveston, Texas; Thomas Lincoln, M.D., Hampden County Correctional Center, Hampden City, Massachusetts; Leigh Lipson, National Association of County and City Health Officials, Washington, D.C.; Grace Macalino, M.D., Brown University Department of Community Health; Fred Maue, M.D., Pennsylvania State Department of Corrections, Camp Hill, PA; Joseph McGarry, M.D., Colorado Department of Corrections, Denver, Colorado; Lynn Mercedes, Minnesota Department of Health, Minneapolis, Minnesota; Amy B. Middleman, M.D., Baylor College of Medicine, Houston, Texas; J. Tom Morgan, J.D., National District Attorney Association, Decatur, Georgia; Joseph E. Paris, M.D., Georgia Department of Corrections, Atlanta, Georgia; David Parr, M.D., University of Texas Medical Branch, Galveston, Texas; John R. Pfister, M.S., Wisconsin State Laboratory of Hygiene, Madison, Wisconsin; Randy Pope, National Association of State and Territorial AIDS Directors, Washington, D.C.; Michael Puisis, D.O., Evanston, Illinois; Aaron Roome, Ph.D., Connecticut Department of Public Health, Hartford, Connecticut; David W. Roush, Ph.D., National Juvenile Detention Association, Albion, Michigan; Tom Saari, M.D., University of Wisconsin Medical School, Madison, Wisconsin; Tamara Serwer, J.D., Southern Center for Human Rights, Atlanta, Georgia; Ronald M. Shansky, M.D., Society of Correctional Physicians, Chicago, Illinois; Frederick E. Shaw, M.D, J.D., Texas Department of Health, Austin, Texas; Gary Shostak, M.P.H., Massachusetts Department of Youth Services, Boston, Massachusetts; Richard Stalder, Louisiana Department of Public Safety and Corrections, Baton Rouge, Louisiana; Jason Stanford, Georgia Department of Human Resources, Atlanta, Georgia; Michelle Staples-Horne, M.D., Georgia Department of Corrections, Atlanta, Georgia; Leah Stockett, Association of State and Territorial Health Officials, Washington, D.C.; David Stoff, Ph.D., National Institutes of Health, Washington, D.C.; Sara Straub, Florida Department of Corrections, Tallahassee, Florida; Betsy Stubblefield, HIV Education Prison Project, Providence, Rhode Island; Thelma Thiel, Hepatitis Foundation International, Cedar Grove, New Jersey; David Thomas, M.D., J.D., Florida Department of Corrections, Tallahassee, Florida; Ann Thomas, M.D., Oregon Health Division, Portland, Oregon; Louis Tripoli, M.D., Spectrum Healthcare Services, St. Louis, Missouri; Theresa Turski, Georgia Department of Human Resources, Atlanta, Georgia; R.J. Verdeyen, American Correctional Association, Lanham, Maryland; John Vertefeuille, Maryland AIDS Administration, Baltimore, Maryland; John Vierling, M.D., Cedars-Sinai Medical Center, Los Angeles, California; Deborah Wexler, M.D., Immunization Action Coalition, St. Paul, Minnesota; Steven Wiersma, M.D., Florida Department of Health, Tallahassee, Florida; Lester N. Wright, M.D., New York State Department of Corrections, Rensselaer, New York; Barry Zack, M.P.H., Centerforce Health Programs, San Quentin, California; Jacqueline Zalumas, Ph.D., Emory University, Atlanta, Georgia.

CDC Consultants: Miriam J. Alter, Ph.D.; Beth P. Bell, M.D.; Amy Khan, M.D.; Linda A. Moyer; Ian A. Williams, Ph.D., Division of Viral Hepatitis, National Center for Infectious Diseases; Douglas Trout, M.D., National Institute for Occupational Safety and Health; Steve Hadler M.D., National Immunization Program; Anne Spaulding, M.D., National Center for HIV, STD and TB Prevention.

Agency Representatives: Dennis Barron, Office of Juvenile Justice and Delinquency Prevention, Washington, D.C.; Alan J. Beck, Ph.D., Bureau of Justice Statistics, Washington, D.C.; Vivian Chen, Sc.D., United State Public Health Service, Washington, D.C.; Amber Hogan, Occupational Safety and Health Administration, Washington, D.C.; Newton E. Kendig, M.D., Federal Bureau of Prisons, Washington, D.C.; Abe Macher, M.D., Health Resources and Services Administration, Rockville, Maryland; Marilyn Moses, National Institute of Justice, Washington, D.C.

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