Cross protective immune responses in mice elicited by prime-boost strategy with a recombinant DNA vaccine and adenoviral 5-based vaccine expressing structural antigens of hepatitis C virus

Abstract

Objective To investigate the development strategy of novel T cell based vaccine against HCV infection. Methods BALB/c mice were primed with pSCK-based DNA vaccine and boosted with type 5 adenoviral vector-based vaccine, which expressed the structural proteins (Core, E1 and E2) derived from a Chinese HCV patient (genotype 1b, Hebei strain). Enzyme linked immunospot assay (ELISPOT) and intracellular cytokine staining (ICS) were used to analyze the elicited antigen-specific immune responses and the efficacy of cross-protection. Results Immunization of mice with the prime-boost vaccination strategy elicited stronger T cell immune responses against multiple HCV antigens than using the DNA vaccines alone, especially the IFN-γ-secreting T cell responses against E1 protein as indicated by ELISPOT assay. ICS data indicated that the prime-boost regimen elicited more TNF-α-producing CD4+ and IFN-γ-producing CD8+ T cells against E1 protein and high levels of IFN-γ-producing CD4+ and CD8+ T cells against E2 protein in comparison with immunization with DNA vaccines. Moreover, the prime-boost vaccination was capable of eliciting effective cross-protection in a surrogate challenge model based on a recombinant heterologous HCV (JFH1, 2a) vaccinia virus. Conclusion The prime-boost vaccination using DNA and rAd5-based vaccine expressing HCV structural antigens induced significant cellular immune response and cross-protection in mice, suggesting the possibility of using it as a promising T cell based vaccine against HCV infection. Key words: Hepatitis C virus; DNA vaccine; rAd5-based vaccine; T cell response; Prime-boost vaccination