Coinoculation with hepatitis B surface and core antigen promotes a Th1 immune response to a multiepitopic protein of HIV‐1

Abstract

Summary It has been defined that strong and multispecific cellular immune responses correlate with a better prognosis during the course of chronic diseases. A cross-enhancing effect on the resulting immune response obtained by the coadministration of recombinant hepatitis B virus (HBV) surface and core Ag was recently observed. With the objective of studying the effect of such Ag on the immune response to coinoculated heterologous Ag and vice versa, several formulations containing the recombinant HBVAg and a multiepitopic protein (CR3) composed by CTL and Th epitopes from HIV-1 were evaluated by s.c. and mucosal administration. Combinations of two and three Ag were evaluated for cellular and humoral immune responses. The results showed that the best Ag combination for nasal immunization was the mixture comprising the CR3 recombinant HIV protein and both HBV Ag. Similarly, it was also the best formulation for s.c. immunization in aluminium phosphate adjuvant. In conclusion, it is possible to induce a Th1 stimulation of the cellular immune response specific for a HIV-based recombinant protein by formulating this Ag with the recombinant HBV Ag.

Two mucosal–parenteral schedules to coadminister a multiantigenic formulation against HIV-1 in Balb/c mice

“…Although, in the case of IgA antibodies the same parameters were superior in the SC + IN group compared with the 2IN&2SC coadministration. The last finding might be relevant because anti-CR3 antibodies cross-react with Env [35] and IgA antibodies can inhibit HIV-1 transcytosis across the mucosal cellular layer [42].…”

“…Although the VLP of hepatitis B include in the multiantigenic formulation provide a Th1 adjuvant effect to the CR3-specific immune response [34,35], it is well known that antibodies against the HBsAg are relevant for protection against hepatitis B disease [59]. Because of that, we also studied the influence of SC + IN and 2IN&2SC coadministrations on the surface antigen-specific humoral response.…”

“…1) is composed of cytotoxic T lymphocyte (CTL) and helper T cell (Th) epitope-rich regions comprising T1 (Env 421-440 , protein location in HXB2 isolate), T2 (Env 105-117 ) and the V3 loop (Env 305-318 ) from gp120, an epitope from gp41 (Env 584-594 ), another from Vpr (Vpr 66-80 ), a fragment of the p66/p51 (reverse transcriptase [RT]) protein (Pol 191-347 ), a part of Nef (Nef 43-150 ), and a part of p24 Gag (Gag 219-307 ) [33]. It was purified from E. coli BL21-CodonPlus(DE3)-RIL (Stratagene, La Jolla, CA) and the purification process was as described previously [35]. A pyrogen-free product with more than 95% purity was achieved.…”

“…The virus-like particles (VLP) of the HBV allows affective nasal and subcutaneous immunization, T helper cell (Th)-1 bias of the CR3-specific response, the induction of CD8+ T cells in the mice spleen and IFN-γ-secreting cells in mesenteric lymph nodes [34]. The anti-CR3 humoral and cellular responses were crossreactive with HIV antigens [34,35]. Previously, we evaluated a regime of immunization with simultaneous subcutaneous-nasal (SC + IN) inoculation of the multiantigenic formulation in each time dose [34].…”

Is there any room for therapeutic vaccination against the HIV-1/AIDS?

“…Previous studies showed that such viruslike particles (VLP) of the HBV provide a Th1 adjuvant effect on the CR3-specific immune-response. 38 According to our studies in mice, the multiantigenic formulation TERAVAC-HIV-1 induces anti-CR3 cellular responses after nasal and parenteral inoculations and best results are obtained in schedules with simultaneous parenteral and nasal co-administration. 38,39 We have found a strong Th1 bias of the CR3-specific response, the induction of CD4 + and CD8 + T cells in mice's spleen and IFN-γsecreting cells in mesenteric lymph nodes.…”