Hepatitis B synthetic immunogen comprised of nucleocapsid T-cell sites and an envelope B-cell epitope.
Previous studies located T-cell recognition of the nucleocapsid of the hepatitis B virus (HBcAg) to residues 120-140 in mice bearing the H-2s or H-2b haplotypes. Herein, we demonstrate that B10.S (H-2s) and B10 (H-2b) H-2 congenic strains recognize distinct T-cell sites within the p120-140 (a synthetic peptide corresponding to residues 120-140 of HBcAg) sequence defined by p120-131 and p129-140, respectively. Peptide p120-131 stimulates B10.S HBcAg-primed T cells, and reciprocally p120-131-primed T cells recognize HBcAg. Similarly, the p129-140 sequence is a T-cell recognition site relevant to the native HBcAg in the B10 strain. It is also shown that these 12-residue peptides efficiently prime T-helper cells, which are capable of eliciting antibody production to HBcAg in vivo. These observations prompted us to examine the ability of the HBcAg-specific p120-140 sequence to function as a T-cell carrier moiety as a component of a totally synthetic hepatitis B vaccine. For this purpose a synthetic B-cell epitope from the pre-S(2) region (p133-140) of the viral envelope was chosen because this sequence represents a dominant antibody-binding site of the envelope. Immunization of B10.S and B10 strains with the synthetic composite peptide c120-140-(133-140) elicited anti-peptide antibody production, which was crossreactive with the native viral envelope. Furthermore, c120-140-(133-140) immunization primed p120-131-specific T cells in the B10.S strain and p129-140-specific T cells in the B10 strain, which recognized HBcAg and provided T-helper cell function for anti-envelope antibody production in vivo. These results demonstrate the feasibility of constructing complex synthetic immunogens that represent multiple proteins of a pathogen and are capable of engaging both T and B cells relevant to the native antigens.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D000939:Epitopes; D006239:Haplotypes; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D051379:Mice; D009842:Oligopeptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D009842:Oligopeptides; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins