Long-term antibody persistence after vaccination with a 2-dose Havrix™ (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions

Abstract

Antibody persistence in two cohorts of adults, who received inactivated hepatitis A (HAV) vaccine (1440El.U; Havrix; GSK Vaccines) according to a 0-6 or 0-12 month schedule in 1992-1993, has been measured annually. After 20 years, >97% of the subjects in both studies were seropositive for anti-HAV antibodies. Geometric mean concentrations in the according-to-protocol cohorts were 312 mIU/ml in 34/36 subjects vaccinated initially at 0-6 months (NCT00289757) and 317 mIU/ml in 85/86 subjects vaccinated at 0-12 months (NCT00291876). Over the whole follow-up period, seven subjects (2+5, respectively) lost circulating anti-HAV antibodies but mounted a strong response after HAV booster administration (1440El.U). Mathematical modelling, which was applied to assess true persistence at Year 20 (accounting for drop-outs and missing data), and to predict longer-term persistence confirmed previous estimates that seropositive anti-HAV levels would persist in ≥95% vaccinees at Year 30 and ≥90% at Year 40. ClinicalTrials.Gov number: NCT00289757/NCT00291876.

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine

“…However, by applying these immunogenicity data for mathematical modeling predicts that at Year 40, ≥ 97% subjects will remain seropositive for anti-HAV antibodies and ≥ 50% subjects will remain ≥ 10 mIU/mL for anti-HBs antibodies. These results are consistent with other studies of long-term anti-HAV and anti-HBs persistence in adults following monovalent vaccine administration 10,13,25 . The percentage of subjects predicted to remain ≥ 10 mIU/mL for anti-HBs does appear to be low.…”

“…Our current results confirm that the vast majority of subjects still present circulating antibodies after 20 y, and suggest that the shallow decrease in GMC is maintained [anti-HAV antibody GMCs: 229.3–511.9 mIU/mL; anti-HBs GMCs: 57.7–249.9 mIU/mL]. Indeed both curves were very similar to the one observed after 20 y of follow-up after primary vaccination of adults with monovalent hepatitis A vaccine 10 . One point of note was that the anti-HAV GMCs were higher in Study A than Study B (significant differences [non-overlapping CIs] from Year 16 and Years 18–20) and were significantly higher from Years 16–20 for anti-HBs GMCs.…”

“…Many studies have already demonstrated long-term immune persistence after monovalent and combined hepatitis A and B vaccination in children, adolescents and adults 10–13,22 . However, even longer term studies are needed to characterize antibody persistence and booster requirements for residents of or travelers to endemic regions.…”

“…Monovalent vaccines against hepatitis A and B are immunogenic and well tolerated 7-9 with long-term immunogenic benefits observed in clinical studies with up to 20 y follow-up 10-13 . Although hepatitis B post-vaccination titers ≥ 10mIU/mL are well established as guaranteeing long-term immunity and protection, the anamnestic responses seen in individuals with lower or non-detectable antibody titers ensure that protection is maintained 14,15 .…”

Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials

“…Various mathematical models have been proposed to predict the long-term decay of antibody levels after vaccination against hepatitis A [23–28], hepatitis B [29], and HPV [30,31]. However, our context, goals, data, and methods were different.…”