Mutated epitopes of hepatitis B surface antigen fused to the core antigen of the virus induce antibodies that react with the native surface antigen.
Fusion of peptide epitopes to the core antigen (HBcAg) of hepatitis B virus (HBV) enhances their immunogenicity, both quantitatively and qualitatively. In a number of vaccine-induced mutants of HBV, glycine145 of the surface antigen S polypeptide (HBsAg) has been replaced by arginine, resulting in loss of cross-reactivity with antibodies to normal (wild-type) HBsAg. HBcAg fusion proteins carrying the immunodominant epitope of HBsAg, in which glycine145 was replaced by arginine, glutamic acid, or lysine, were produced in Escherichia coli and formed particles that displayed HBc antigenicity and immunogenicity similar to that of HBcAg itself. The fusion proteins also elicited T-cell proliferative responsiveness to HBcAg and HBsAg. Fusions carrying either wild-type or mutated epitopes of HBsAG showed HBs antigenicity in immunoblot analysis and antigen-capture immunoradiometric assay, but both mutant and wild-type derivatives induced antibodies that cross-reacted with wild-type HBsAG. The results emphasise the potential for HBcAg fusion proteins in vaccines by broadening the antibody response in a way that could confer protection against both wild-type and variant form of HBV.
Shiau
A L
AL
Institute of Cell and Molecular Biology, University of Edinburgh, Scotland.
Murray
K
K
D000818:Animals; D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D001120:Arginine; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D004926:Escherichia coli; D005998:Glycine; D006510:Hepatitis B Antibodies / Q000096:biosynthesis* / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D011993:Recombinant Fusion Proteins; D001120:Arginine; D005998:Glycine