Hepatitis A Prevention, Immunization : Vaccine, Part 3

by CDC

(Page 9 of 13)

Vaccination Schedules. Results of multiple studies indicate that, among adults administered hepatitis A vaccine according to a schedule that mixed the two currently licensed vaccines, the proportion that subsequently had protective antibody levels did not differ from that of adults vaccinated according to the licensed schedules, and final GMCs were high. Although using the vaccines according to the licensed schedule is preferable, on the basis of the similar immunogenicity of both vaccines in adults and children, these data indicate that the two brands of hepatitis A vaccine can be considered interchangeable.

Limited data are available regarding response to a delayed second vaccine dose. In one study, 85 (97%) of 88 persons aged >18 years who had received 1 dose of VAQTA (50 U) had anti-HAV levels >10 mIU/mL 18 months later. None reported a history of hepatitis A, and all responded to a second dose. Final GMCs were not different compared with persons vaccinated according to a 0-, 6-month schedule. In another study, 132 (84%) of 156 persons aged 1 month - 64 years who had responded to 1 dose of HAVRIX (720 EL.U. for children aged < 18 years; 1,440 EL.U. for adults) had anti-HAV levels >20 mIU/mL a mean of 27 months later. None of these persons reported a history of hepatitis A. All but one of these persons responded to a second dose, with a substantial rise in antibody levels. In a third study, 18 (72%) of 25 adults who had received 1 dose of HAVRIX 4 - 8 years previously had anti-HAV levels >10 mIU/mL, and all 25 responded to a second dose of vaccine with a substantial increase in anti-HAV levels.

Factors Associated with Reduced Immunogenicity. The presence of passively acquired anti-HAV at the time of vaccination appears to diminish the immune response. Administration of IG concurrently with the first dose of hepatitis A vaccine did not decrease the proportion of adults who subsequently had protective levels of antibody compared with adults who had been administered hepatitis A vaccine alone, but GMCs of adults who received IG were substantially lower 1 month after completion of the vaccine series than GMCs of adults who had been administered hepatitis A vaccine alone. However, their antibody levels were >100-fold higher than levels considered to be protective, suggesting that the reduced immunogenicity of hepatitis A vaccine that occurs with concurrent administration of IG is not clinically significant in the short term. The effect of reduced GMCs on long-term protection is unknown.

Reduced vaccine immunogenicity also has been observed in infants who had passively acquired antibody because of previous maternal HAV infection and were administered hepatitis A vaccine according to a number of different schedules. In the majority of studies, all infants subsequently had protective levels of antibody, but the final GMCs were approximately one third to one tenth those of infants born to anti-HAV - negative mothers and vaccinated according to the same schedule. Infants with passively acquired antibody who receive hepatitis A vaccine had substantially lower concentrations of anti-HAV 6 years later compared with vaccinated infants with no passively acquired antibody. Despite lower antibody levels after the primary series, the majority of infants with passively acquired antibody had an anamnestic response to a booster dose 1 - 6 years later. Passively acquired antibody declines to undetectable levels in the majority of infants by age 1 year. Hepatitis A vaccine is highly immunogenic for children who begin vaccination at age >1 year, regardless of maternal anti-HAV status.

Hepatitis A vaccine using a standard dose and schedule is immunogenic for children and adults with HIV infection. Those with higher CD4 counts (>300 cells/mm3) respond nearly as well as persons who are not immunocompromised, but adults with lower CD4 counts are less likely to acquire protective levels of antibody. Protective levels of antibody developed after vaccination in 61% - 87% of HIV-infected adults and in 100% of 32 HIV-infected children. Lower CD4 cell count at the time of vaccination, but not the CD4 cell count nadir, was associated with lack of response, suggesting that immunologic reconstitution with highly active antiretroviral therapy might restore the ability to respond to vaccination.

Vaccination of children or adults with chronic liver disease of viral or nonviral etiology produced seroprotection rates similar to those observed in healthy adults. However, final antibody levels were substantially lower for each group of chronic liver disease patients than for healthy adults. Immunogenicity in liver transplant recipients has varied among studies. In one study, none of the eight patients who had received a liver transplant responded to hepatitis A vaccination; in another study, only six (26%) of 23 liver transplant recipients responded. However, hepatitis A vaccine was immunogenic for liver transplant patients in another study, with 38 (97%) responding to a standard dose and schedule. Only 28 (72%) of 39 kidney transplant recipients in this study subsequently had protective levels of antibody. A follow-up study indicated that antibody levels might decline more rapidly for both liver and kidney transplant recipients compared with typical rates of decline for healthy patients.

Limited data indicate that age might reduce the immunogenicity of hepatitis A vaccine. In certain studies, the proportion of persons aged >40 years who had protective antibody levels was similar to that of persons aged <4 0 years, but final antibody levels were lower in the older age group. Additional factors associated with decreased immunogenicity to other vaccines (e.g., smoking and obesity) have not been evaluated for the currently licensed formulations of hepatitis A vaccine. No data are available pertaining to response rates to revaccination among persons who do not respond to the primary vaccine series.

Simultaneous Administration with Other Vaccines. Limited data from studies conducted among adults indicate that simultaneous administration of hepatitis A vaccine with diphtheria, poliovirus (oral and inactivated), tetanus, typhoid (both oral and IM), cholera, Japanese encephalitis, rabies, or yellow fever vaccines does not decrease the immune response to either vaccine or increase the frequency of reported adverse events. Studies indicating that hepatitis B vaccine can be administered simultaneously with hepatitis A vaccine without affecting either vaccine's immunogenicity or increasing the frequency of adverse events led to the licensure of TWINRIX. Studies conducted among infants and young children aged < 18 months have demonstrated that simultaneous administration of hepatitis A vaccine with diphtheria-tetanus-acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), hepatitis B, MMR, or inactivated poliovirus vaccines does not affect the immunogenicity and reactogenicity of these vaccines.

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