Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered in to the cDNA of HBsAg-S at a position corresponding to the exposed site with in the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable regio n 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodomin ant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins wer e synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region expo sed on the particles retained an antigenic structure similar to that recogn ized immunologically during natural infection. VLPs containing epitopes fro m either HCV-1a or -1b strains were produced that induced strain-specific a ntibody responses in immunized mice. Injection of a combination of these VL Ps induced antibodies against both HVR1 epitopes that resulted in higher ti ters than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant part icles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.