Immunological characteristics of a recombinant hepatitis B virus-derived multiple-epitope polypeptide: a study in polyvalent vaccine design.

Immunological properties of a model polyepitope immunogen (MEP-1) consisting of selected determinants from envelope proteins of hepatitis B virus (HBV) were examined. Immunization with MEP-1 induced high-titre antibodies in a variety of murine strains and in rabbits although an overall hierarchy of B-cell immunodominance was observed as pre-S1-derived > S-derived > pre-S2-derived segments. Anti MEP-1 antibody responses in all hosts were found to be exclusive for HBV-derived sequences in the absence of any fraction directed against the various interepitope junctions. With panels of overlapping peptides it was observed that the anti-pre-S1 and anti-pre-S2 components of anti-MEP-1 antibodies were, in all animals tested, of the desired specificity from the standpoint of potential virus-neutralizing ability. The MEP-1 segment representing residues 124-127 of the major protein of hepatitis B surface antigen (HBsAg) was found to elicit a conformation-specific antibody response. Furthermore, this subpopulation was either predominantly or exclusively against the Met133-Lys141-dependent group-specific epitope. Finally, the HBV sequences in MEP-1 were shown to retain their Th-cell activities. These studies suggest that MEP-1 provides a useful tool in the study of polyvalent vaccine design.