Correspondence
Hepatitis A Vaccination
N Engl J Med 1998; 339:705September 3, 1998
- Article
To the Editor:
Werzberger et al. (April 16 issue)1 report that on the basis of six years of follow-up after the Monroe efficacy trial, vaccination against hepatitis A is protective. However, it still remains to be determined how long the vaccine will be effective. We know that the level of antibody after immunization with either one of the commercially available vaccines is much lower than the level associated with natural infection. Standard assays with a lower limit of detection of 100 mIU per milliliter usually fail to detect vaccine-induced levels of hepatitis A virus antibody. Once there has been exposure to a viral antigen, however, even very low levels of antibody (e.g., <20 mIU per milliliter) can be neutralizing in vaccinated persons.2 According to estimates of the persistence of antibody that are derived from kinetic models, protective levels of antibody could be present for many years. Roughly 40 percent of the vaccine recipients will have detectable antibody levels after 30 years.3
The degree and duration of protection against hepatitis A, however, depend on the age and immune status of the vaccine recipient. The seroconversion rate is lower in persons who are positive for the human immunodeficiency virus than in those who are negative for it.4 In comparison with children, vaccinated adults have a greater decrease in the antibody titer over time. The elderly population in the United States is especially at risk and has been found to have a much higher case fatality rate (2.7 percent in persons over 49 years old) than the general population (0.3 percent). This group will become increasingly more susceptible to the disease because of the decreasing rate of antibody to hepatitis A virus among older Americans.5 A key issue that has not yet been resolved involves recommendations for the timing of extra booster doses of vaccine in persons no longer likely to have detectable levels of antibody.
5 ReferencesMichael P. Thomas, M.D.
New England Medical Center, Boston, MA 021111
Werzberger A ,Kuter B ,Nalin D . Six years' follow-up after hepatitis A vaccination. N Engl J Med 1998;338:1160-1160
Full Text | Web of Science | Medline2
Lemon SM ,Binn LN . Serum neutralizing antibody response to hepatitis A virus. J Infect Dis 1983;148:1033-1039
CrossRef | Web of Science | Medline3
Wiens BL ,Bohidar NR ,Pigeon JG , et al. Duration of protection from clinical hepatitis A disease after vaccination with VAQTA. J Med Virol 1996;49:235-241
CrossRef | Web of Science | Medline4
Hess G ,Clemens R ,Bienzle U ,Schonfeld C ,Schunck B ,Bock HL . Immunogenicity and safety of an inactivated hepatitis A vaccine in anti-HIV positive and negative homosexual men. J Med Virol 1995;46:40-42
CrossRef | Web of Science | Medline5
Hadler SC. Global impact of hepatitis A virus infection: changing patterns. In: Hollinger FB, Lemon SM, Margolis HS, eds. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins, 1991:14-20.
Author/Editor Response
Dr. Nalin replies:
To the Editor: The basis of long-term protection against recurrent hepatitis A in naturally immune persons is immune memory, whether or not detectable antibody persists, as was demonstrated by Villarejos and coworkers.1 Vaccine recipients, like naturally immune study subjects, possess immune memory, which is induced by a single priming dose of hepatitis A vaccine.2 On reexposure to hepatitis A antigen (either through a booster dose of vaccine or after viral transmission),1,3 immune-memory cells induce a rapid anamnestic rise in neutralizing antibody early in the incubation period of hepatitis A virus infection; such anamnestic antibody is (like immune globulin injection) capable of preventing clinically apparent disease. Since during much of the period of protection afforded by immune globulin, levels of hepatitis A antibody are below the limit of detectability with current sensitive tests,4 it is possible that vaccine recipients with apparent seroreversion still have protective (but undetectable) neutralizing antibody. Nevertheless, in more than 99 percent of vaccine recipients, including 2-to-17-year-olds and 18-to-75-year-olds, the booster dose is followed quickly by an anamnestic antibody rise (even in persons with seroreversion).2 Although the increase in antibody is lower in adults than in children, it exceeds antibody titers provided by immune globulin by such a high factor4 that the difference is not clinically significant; paradoxically, memory-cell responses in adults exceed those in children.5
Our studies dealt with nonimmunosuppressed vaccine recipients. Certainly, immunosuppressed persons require further study to assess the induction and persistence of immunologic memory and the possible need for periodic boosters.
5 ReferencesDavid R. Nalin, M.D.
Merck Vaccine Division, West Point, PA 19486-00041
Villarejos VM ,Serra J ,Anderson-Visona K ,Mosley JW . Hepatitis A virus infection in households. Am J Epidemiol 1982;115:577-586
Web of Science | Medline2
Nalin DR . Vaqta: hepatitis A vaccine, purified inactivated. Drugs Future 1995;20:24-293
Werzberger A ,Kuter B ,Nalin D . Six years' follow-up after hepatitis A vaccination. N Engl J Med 1998;338:1160-1160
Full Text | Web of Science | Medline4
Shouval D ,Ashur Y ,Adler R , et al. Single and booster dose responses to an inactivated hepatitis A virus vaccine: comparison with immune serum globulin prophylaxis. Vaccine 1993;11:Suppl 1:S9-S14
CrossRef | Web of Science | Medline5
Chen XO ,de Gast GC ,Wang RX ,Boland GJ ,Nalin DR ,van Hattum J . B cell memory after hepatitis A vaccination, using 2 or 3 doses. Hepatology 1997;26:Suppl:432A-432A abstract.
CrossRef | Web of Science
- Citing Articles (3)
Citing Articles
1
Mehmet Arslan, Russell H. Wiesner, John J. Poterucha, Nizar N. Zein. (2001) SAFETY AND EFFICACY OF HEPATITIS A VACCINATION IN LIVER TRANSPLANTATION RECIPIENTS1, 2. Transplantation 72:2, 272-276
CrossRef2
Mehmet Arslan, Russell H. Wiesner, John J. Poterucha, B.John Gross, Nizar N. Zein. (2000) Hepatitis A antibodies in liver transplant recipients: Evidence for loss of immunity posttransplantation. Liver Transplantation 6:2, 191-195
CrossRef3
J.B. Cederna, D. Klinzman, J.T. Stapleton. (1999) Hepatitis A virus-specific humoral and cellular immune responses following immunization with a formalin-inactivated hepatitis A vaccine. Vaccine 18:9-10, 892-898
CrossRef
