Introduction: Cellular immunity to HIV-1 is essential for viral control. Currently, most vaccine candidates in clinical trials were developed to stimulate HIV-specific CD8+ and CD4+ cells. Additionally, the knowledge of the natural infection emphasizes the importance of the mucosal immunity. Consequently, it is important to develop vaccine candidates for an effective mucosal immunization. We developed a vaccine formulation (TERAVAC) using a recombinant multiepitopic protein (CR3), which comprises CTL and Th epitope rich regions of HIV-1 co-inoculated with the surface (HBsAg) and core (HBcAg) antigens of the hepatitis B virus (HBV) as adjuvant.

Materials and Methods: Recombinant antigens CR3, HBcAg and HBsAg were >95% purity. Humoral responses were tested by ELISA and western blot. The frequency of IFN-g-secreting cells assessed by ELISPOT assay and proliferation of CD4+ and CD8+ cells by CFSE staining and flow cytometry.  

Results: In mice, the nasal-subcutaneous co-administration of TERAVAC induced a Th1-biased specific response against CR3, CD8+ T cells in spleen and IFN-g-secreting cells in mesenteric lymph nodes, cross-reactive p24-specific IFN-g-secreting cells in spleen and Nef-specific antibodies which might avoid the toxic effects of this antigen. Additionally, we observed anti-HBsAg and anti-HBcAg cellular and humoral responses. 

Conclusions: This study provided proof of the concept that nasal-subcutaneous co-administration of the recombinant protein CR3 with the Ags of HBV stimulates HIV-specific cellular and humoral responses. A prominent aspect of this strategy is that it considers evolving scenarios in areas where a high incidence of HBV infection is reported. TERAVAC is currently tested in a phase I clinical trial.