Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes

- HIV-1 antigen-specific IFN-γ responses were detected in mice immunized with rSFV2gen-based VRP constructs.
- Gag-specific TNF-α and Env-specific IL-2 T cell responses were also detected in mice receiving VRP constructs.
- Combinatorial vaccine stimulated Gag and Pol-specific IFN-γ and Pol-specific TNF-α T cell response in immunized mice.
- HIV-1C antigen-specific antibodies were elicited in mice receiving the Gag and Env VRP constructs.
- SFV2gen-based VRP constructs are highly immunogenic and promising candidates for HIV vaccine development.

Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the clade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-γ T cell responses as detected by the ELISPOT assay. Additionally, Gag-specific TNF-α secreting CD8+ and CD4+ T cells and Env-specific IL-2 secreting T cells were also elicited by mice immunized with Gag and Env constructs, respectively, as estimated by intracellular cytokine staining assay. Moreover, an HIV Pol-specific TNF-α response was elicited in mice immunized with a combination of the three VRP constructs. Furthermore, HIV-1C Gag and Env-specific binding antibodies were elicited as verified by gp120 ELISA and p24 Gag ELISA, respectively. The immunogenicity of VRPs was found to be higher as compared to that of RNA replicons and VRPs may therefore be promising preventive and therapeutic candidate vaccines for the control and management of HIV/AIDS.