Abstract
ABSTRACTVaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16–20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.
Highlights
Infections caused by the hepatitis A virus (HAV) and hepatitis B virus (HBV), which occur across the globe, are associated with significant morbidity and mortality, as well as inflicting a considerable healthcare burden.[1,2,3]
The long-term according-to-protocol (LT-ATP) cohort for immunogenicity was restricted to fully vaccinated subjects who were seronegative before vaccination
#The eligibility checks for these subjects were originally performed using ELISA, the concentrations presented in the table are the CLIA re-test results ÃAnti-HAV anamnestic response defined as anti-HAV antibody concentrations one month post-challenge: either 15 mIU/mL in subjects, seronegative at pre-challenge; or 2-fold increase in subjects with pre-challenge anti-HAV antibody concentrations 100 mIU/mL; or 4-fold increase in seropositive subjects having pre-challenge anti-HAV antibody concentrations
Summary
Monovalent vaccines against hepatitis A and B are immunogenic and well tolerated[7,8,9] with long-term immunogenic benefits observed in clinical studies with up to 20 y follow-up.[10,11,12,13] hepatitis B post-vaccination titers 10mIU/mL are well established as guaranteeing longterm immunity and protection, the anamnestic responses seen in individuals with lower or non-detectable antibody titers ensure that protection is maintained.[14,15] For hepatitis A, as the inactivated vaccines induce early post-vaccination circulating antibodies 100- to 1000-fold higher than those associated with clinical protection,[14] and as anti-HAV titers following vaccination are around 5–6000 mIU/mL, but fall rapidly to 500–1000, a subject is considered protected after vaccination when antibodies are detectable. Due to the considerable overlap of risk factors and areas of high endemicity for both diseases, a combined vaccine against both viruses represents a pragmatic approach that reduces the number of vaccine administrations, in particular for travelers.[16]
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