Anti-HIV-1 and anti-HBV immune responses in mice after parenteral and nasal co-administration of a multiantigenic formulation.

The cell-mediated immune response to HIV-1 is an essential element of the mechanisms for viral replication control. Currently, most of the vaccine candidates in clinical trials were developed to stimulate HIV-1-specific CD8+ cytotoxic (CTL) and CD4+ T helper (Th) lymphocytes. We have been working on a novel approach to develop a vaccine formulation for HIV-1 using a recombinant multiepitopic protein (named CR3), which comprises CTL and Th epitope-rich regions of HIV-1 from several subtype B isolates, co-inoculated with the hepatitis B virus surface (HBsAg) and core (HBcAg) antigens of the hepatitis B virus (HBV) as adjuvant. According to our studies in mice, the nasal-subcutaneous co-administration of this multiantigenic formulation induces a strong Th1-biased specific response against CR3, CD8+ T cells in mice spleen and IFN-gamma-secreting cells in mesenteric lymph nodes. Cross-reactive p24-specific IFN-gamma-secreting cells in spleen were also detected. Moreover, Nef-specific antibodies were elicited in mice sera which might avoid the toxic effects of this antigen. However, a marginal anti-CR3 antibody response was elicited in vaginal mucosa. Additionally, we observed anti-HBsAg and anti-HBcAg cellular and humoral responses. In this regard, our multiantigenic formulation might provide immunity against HBV as an additional benefic considering the high HIV-1-HBV co-infection rate reported worldwide.