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.
Manivel
V
V
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Ramesh
R
R
Panda
S K
SK
Rao
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011233:Precipitin Tests; D011487:Protein Conformation; D011817:Rabbits; D014614:Vaccines, Synthetic
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D046911:Macromolecular Substances; D010455:Peptides; D014614:Vaccines, Synthetic