A synthetic peptide spontaneously self-assembles to reconstruct a group-specific, conformational determinant of hepatitis B surface antigen.

A cysteine-rich peptide of sequence 124 to 147 of the major protein of hepatitis B surface Ag (HBsAg) was synthesized. On cleavage and subsequent work-up it was found that all of the cysteine sulfhydryl groups had spontaneously formed disulfide bonds to yield a heterogenous mixture of multiple forms with molecular masses ranging from 8 to 35 kDa (peptide OS[124-147]). In a direct ELISA peptide OS[124-147] showed a high degree of cross-reactivity with polyclonal anti-HBsAg antiserum whereas the HBsAg-related antigenicity of its disulfide-reduced analogs was insignificant. Peptide OS[124-147] was also recognized by all 15 of the anti-HBsAg-positive human sera tested. Further studies revealed that peptide OS[124-147] represents the conformational, disulfide-dependent "a" determinant of HBsAg and elicits antibodies that cross-react with a variety of HBsAg subtypes. Anti-peptide antibodies bound to the corresponding native epitope with an apparent affinity higher than that of homologous antisera. Finally, polyclonal anti-OS[124-147] antibodies could also immunoprecipitate purified Dane particles in solution. Together these studies indicate that peptide OS[124-147] represents an excellent candidate component of a peptide-based vaccine for hepatitis B.