Vaccine engineering: enhancement of immunogenicity of synthetic peptide vaccines related to hepatitis in chemically defined models consisting of T- and B-cell epitopes.
We report the development of two models for synthetic hepatitis B vaccines. The models were based on the multiple antigen peptide (MAP) system and contained the relevant B- and T-cell epitopes without any macromolecular carrier. Two peptides, representing the a determinant of the S region (S protein) of hepatitis B surface antigen, a dominant serotype of hepatitis B virus infection found in humans, and residues 12-26 of the pre-S(2) region of the middle protein were incorporated as either monoepitope or diepitope MAP models. Immunizations of outbred rabbits with the monoepitope MAP that contains the pre-S(2) antigen resulted in high-titered antibody response to the middle protein, but the other monoepitope, containing only the a-determinant peptide antigen, resulted in poor immune responses to either the peptide antigens or to the S protein. The diepitope MAPs containing both the a and the pre-S(2) determinants produced high-titer antibodies reactive to the a-synthetic peptide and the S protein, as well as to the middle proteins. Thus, our results show that the diepitope MAP models eliminate the need for a protein carrier and that the pre-S(2) peptide determinant serves as a T-helper cell epitope that enhances the immune response of the S region and overcomes the poor immunogenicity encountered with a single epitope of the S region.
Tam
J P
JP
Rockefeller University, New York, NY 10021.
Lu
Y A
YA
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D004220:Disulfides; D000939:Epitopes / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines; D007202:Indicators and Reagents; D008954:Models, Biological; D010455:Peptides / Q000138:chemical synthesis; D011817:Rabbits / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D004220:Disulfides; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007202:Indicators and Reagents; D010455:Peptides; D014612:Vaccines; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines