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-I) cons isting of selected determinants from envelope proteins of hepatitis B virus (HBV) were examined. Immunization with MEP-I induced high-titre antibodies in a variety of murine strains and in rabbits although an o verall hierarchy of B-cell immunodominance was observed as pre-S1-deri ved > S-derived > pre-S2-derived segments. Anti MEP-I antibody respons es in all hosts were found to be exclusive for HBV-derived sequences i n the absence of any fraction directed against the various interepitop e junctions. With panels of overlapping peptides it was observed that the anti-pre-Si and anti-pre-S2 components of anti-MEP-1 antibodies we re, in all animals tested, of the desired specificity from the standpo int of potential virus-neutralizing ability. The MEP-I segment represe nting residues 124-127 of the major protein of hepatitis B surface ant igen (HBsAg) was found to elicit a conformation-specific antibody resp onse. Furthermore, this subpopulation was either predominantly or excl usively against the Met133-Lys141-dependent group-specific epitope. Fi nally, the HBV sequences in MEP-I were shown to retain their Th-cell a ctivities. These studies suggest that MEP-I provides a useful tool in the study of polyvalent vaccine design.