Anti-HBs after hepatitis B immunization with plasma-derived and recombinant DNA-derived vaccines: binding to mutant HBsAg

The G145R mutant of the small S-protein is a major escape mutant of hepatit is B virus observed in natural infection, after immunization and HBIG thera py. In a previous study we found that plasma-derived and recombinant DNA-de rived vaccine HBsAg reacted differently with monoclonal antibodies sensitiv e for the G145R change. In the present study we investigated the binding of polyclonal anti-HBs obtained after immunization with plasma vaccine and re combinant DNA vaccine to synthetic peptides (adw(2), adr) and rHBsAg (HepG2 ) (ayw(3); wild type and a 145R mutant). Anti-HBs binding to synthetic pept ids (25-mere, 7aa overlap) from the "a"-loop was significantly reduced by t he G145R substitution and by changing the amino acid sequence from adw(2) i nto adr. With mutant G145R rHBsAg the inhibitory activity of vaccine anti-H Bs was decreased compared to rHBsAg wild type. In general only minor differ ences were observed between plasma vaccine and recombinant DNA vaccine rela ted antibody responses. However, the individual heterogeneity in epitope sp ecific reactivity with its possible consequences for protection (against es cape mutants) is not reflected in an anti-HBs titer by standard anti-HBs as says. The presented differentiation in anti-HBs response after immunization may deliver new tools for evaluation of future vaccines. (C) 2001 Elsevier Science Ltd. All rights reserved.