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

Vaccination 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 (TM), GSK Vaccines, Belgium) at 0-1-6months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20y (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 (TM)/Engerix (TM)-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20y, 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 40y 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.