G2 Dendrimer as a Carrier Can Enhance Immune Responses Against HCV-NS3 Protein in BALB/c Mice

Background: Hepatitis C virus (HCV) infection is a major issue of public health. It seems of paramount importance to find an effective vaccine against HCV infection. The best vaccine candidate should induce robust cellular responses. The aim of the current study was to evaluate immunogenicity effects of novel conjugated dendrimer G2 with the recombinant NS3 antigen as a vaccine candidate for eliciting Th1-oriented cellular responses.

Methods: Female BALB/c mice were immunized with different regimes especially with NS3 conjugated with G2 dendrimer. The humoral responses (Total IgG and IgG iso-typing) and cellular responses (Ex vivo IFN-γ and IL-4 ELISpot assays, in vitro CTL assay and proliferation) were evaluated and compared in immunized mice.

Results: The results indicated that induced specific total IgG in all mice groups immunized with rNS3 formulated with different adjuvants and IgG2a subclass was the predominant isotype in rNS3-G2 (p≤0.05). For preliminary evaluation of cellular response, ex vivo ELISpot assay has shown that the higher frequency of IFN-γ producing cells was in groups immunized with rNS3+M720 and rNS3-G2 (p= 0.0012) than control groups. Finally, the rNS3-specific CTLs activity showed the highest percentage of specific lysis (LDH release) of the target cells in rNS3-G2 and rNS3+M720 groups.

Conclusion: In the present study, as our knowledge, this is first time that the immunogenicity of nanodendrimer G2 as a biocompatible adjuvant with the HCV-NS3 antigen was evaluated. The results showed high capability of the regimen to induce strong Th1-orinted cellular response in mice model, indicating the dendrimer G2 as a novel adjuvant candidate for HCV vaccine studies.