title: Anti-HBs after hepatitis B immunization with plasma-derived and recombinant DNA-derived vaccines: binding to mutant HBsAg.
abstract: The G145R mutant of the small S-protein is a major escape mutant of hepatitis B virus observed in natural infection, after immunization and HBIG therapy. In a previous study we found that plasma-derived and recombinant DNA-derived vaccine HBsAg reacted differently with monoclonal antibodies sensitive for the G145R change. In the present study we investigated the binding of polyclonal anti-HBs obtained after immunization with plasma vaccine and recombinant DNA vaccine to synthetic peptides (adw(2), adr) and rHBsAg (HepG2) (ayw(3); wild type and a 145R mutant). Anti-HBs binding to synthetic peptids (25-mers, 7aa overlap) from the "a"-loop was significantly reduced by the G145R substitution and by changing the amino acid sequence from adw(2) into adr. With mutant G145R rHBsAg the inhibitory activity of vaccine anti-HBs was decreased compared to rHBsAg wild type. In general only minor differences were observed between plasma vaccine and recombinant DNA vaccine related antibody responses. However, the individual heterogeneity in epitope specific reactivity with its possible consequences for protection (against escape mutants) is not reflected in an anti-HBs titer by standard anti-HBs assays. The presented differentiation in anti-HBs response after immunization may deliver new tools for evaluation of future vaccines.
authors.affiliation: Department of Virology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands. heijtink@viro.fgg.eur.nl
authors.forename: R A
authors.initials: RA
authors.lastname: Heijtink
authors.forename: P
authors.initials: P
authors.lastname: van Bergen
authors.forename: M H
authors.initials: MH
authors.lastname: van Roosmalen
authors.forename: C M
authors.initials: CM
authors.lastname: Sünnen
authors.forename: W P
authors.initials: WP
authors.lastname: Paulij
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
authors.forename: A D
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000378:metabolism*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D009154:Mutation; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA