Evaluation of the immunogenicity of recombinant replicative DNA vaccines expressing multiple antigens of hepatitis C virus in a mice model

Abstract

Objective To investigate the immunogenicity and cross protective effects of two novel HCV DNA vaccines in a mice model. Methods Two self-replicating alphavirus vector-based HCV DNA vaccines, pSCK CE1E2Y and pSCK H155, were constructed based on the genes encoding the structural proteins (Core, E1 and E2) and structural and NS3 fusion proteins (Core, E1 , E2 and NS3) of a HCV strain isolated from a Chinese patient (genotype 1b, Hebei strain), respectively. Western blot analysis was performed to detect the expression of fusion antigens. The BALB/c mice were intradermally immunized with the recombinant DNA vaccines by using electroporation. The immune responses induced in mice and the cross protective effects of the recombinant DNA vaccines were evaluated. Results The DNA vaccines effectively expressed the target antigens in vitro. The antigen-specific antibody responses and specific T cell immune responses were induced in mice by the immunization of replicative DNA vaccines. However, no effective cross protection was provided by either of the DNA vaccines in the surrogate challenge model based on a recombinant heterologous HCV (JFH1, 2a) vaccinia virus strain. Conclusion Although no effective cross protection was observed, both of the two replicative DNA vaccines could induce strong humoral and cellular immune responses against multi-target antigens of HCV strains. This study has paved the way for further investigation on the development of novel HCV vaccines. Key words: Hepatitis C virus; Replicative DNA vaccine; Fusion antigen; T cell response