Priming hepatitis B surface [HBsAg]- and core antigen [HBcAg]- specific immune responses by chimeric, HBcAg with a HBsAg 'a' determinant

ABSTRACT

We developed an immunogen to stimulate multivalent immunity against hepatitis B surface antigen [HBsAg] and hepatitis B core antigens [HBcAg]. Immune responses specific for both HBsAg and HBcAg play an important role in controlling the infection. HBsAg-specific antibodies mediate elimination of virions at an early stage of infection and prevent the spread of virus. The immunogen was constructed by inserting the immunodominant, antibody-binding 'a' determinant [aa 111-149] of HBsAg [with or without a poly-glycine [PG] linker] into the e2 epitope of HBcAg. Only the constructs in which the HBsAg 'a' determinant was inserted into HBcAg, flanked by PG linkers, expressed a chimeric protein in human embryonic kidney cells with HBsAg and HBcAg antigenicity. Both glycosylated and non-glycosylated forms of the chimeric protein were immunoprecipitated from cell lysate. Intramuscular DNA vaccination of mice with plasmids expressing chimeric HBcAg primed antibody responses against well-defined serologically-defined determinants of both, native HBcAg, and native HBsAg. In addition, CD8[+] T cell responses against HBcAg epitopes were primed by this chimeric HBV antigen. The e2 sequence of HBcAg can thus be used to present heterologous epitopes without loss of immunogenicity of the HBcAg protein