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.
Kumar
A
A
Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Kumar
V
V
Shukla
G C
GC
Rao
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D000939:Epitopes / Q000276:immunology; D005260:Female; D017325:Hepatitis B Vaccines / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000939:Epitopes; D017325:Hepatitis B Vaccines; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C073096:multiple-epitope polypeptide 1, Hepatitis B virus