Long-term immunity after hepatitis B vaccination.

Abstract

I read with interest the article by Metodi et al. In a cross-sectional study, the authors found that more than two-thirds of children under 5 years age who had received DPTHB at 4, 8 and 12 weeks of age had protective anti-HBs levels. On this basis, they suggested changes in the hepatitis B immunisation schedule. A few points require comment. The authors found a lower rate of seroprotection in vaccinated children than in those reported from The Gambia and Turkey. They postulated that the variation might be owing to differences in immunisation schedules, with the birth dose being included in both of the latter studies which included younger children than in their study. However, this is not necessarily true if we consider some recent studies. One half of the children who received a birth dose of hepatitis B vaccine did not have evidence of immune memory as measured by development of anamnestic responses to the booster dose 15 years after vaccination. In another study, 5 years after immunisation with a hexavalent vaccine at 3, 5 and 11 months of age, immunological memory was found to have persisted, suggesting that booster doses are not needed. So neither the sero-protection nor the duration of immunity depends upon the schedule administering a birth dose of vaccine. Antibody persistence and duration of protection against infection are directly proportional to the peak antibody concentration after primary immunisation. Although most children with low peak concentrations lose their antibodies within a few years, they are not at risk of hepatitis as long as they have immunological memory for HBsAg. Memory persists beyond the time at which antibodies are present and protects against disease. The authors’ suggestion of a change in the HB immunisation schedule including a dose immediately after birth to improve immunity is also not supported, as found by our study. In a randomised trial comparing two hepatitis B vaccination schedules (0, 6 and 14 weeks and 6, 10 and 14 weeks), we found that 97.3% of infants in the former group were sero-protected with a geometric mean anti-HBs titre (GMT) of 113.78 mIU/ml vs 94.6% in the latter group (GMT 107.04 mIU/ml) (p50.8). Many other studies which include the birth dose of vaccine have reported similar results, although they have used different schedules. The authors also state that immunological response to the HBV vaccine increases with increasing intervals between the first and third doses, but it is the interval between the second and third doses of vaccine which is associated with improved immunity. Usually, the first two doses are sufficient to initiate the production of antibodies against HBsAg, thereby priming the immune system for a secondary response. The third dose stimulates this secondary response, resulting in a further accelerated response and higher antibody titre than after the first two doses. This is the basis for the conventional 0, 1, 6 months schedule. Finally, the authors’ description of reduced response to HBV vaccine in preterm infants (leading to a lower proportion of children with protective anti-HBs levels in the current study) and improved seroconversion if the first dose is delayed to Annals of Tropical Paediatrics (2011) 31, 279–280