Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers

Abstract

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.

Figures

Figure 1. Study design.

Figure 2. Evolution of anti-HBs geometric mean concentrations in boosted and unboosted groups (LT-ATP immunogenicity cohort). Boosted group: Subjects who received booster dose at year 5 (month 60). Unboosted group: Subjects who did not receive the booster dose at year 5 (month 60). Note: At year 9 the results of only 10 subjects were included in the analysis- hence this time point should not be taken into account to assess the kinetic of the immune response. This limited number of subjects was due to logistic problems during the conduct of the study which resulted in fewer subjets being loaded into the database. From the commencement of primary vaccination until follow-up year 10, anti-HBs antibodies were measured using AUSAB RIA (Abbott Laboratories). *Assay change from year 11 until year 16: Antibodies were measured using AUSAB EIA (Abbott Laboratories, IL, USA). ^Assay change from year 17 until year 20: Antibodies were measured using an in-house validated ELISA.

Figure 3. Serum antibody concentrations at the pre- and post-challenge dose time-point (Long-term ATP cohort for immunogenicity) in the groups boosted and unboosted at year 5. Each box shows the median (horizontal line), quartile range (the box itself), and high (97.5%) and low (2.5%) (whiskers).