Pharmacodynamics Of Ad5-HIVgp160Vaccine And IL15Gene Adjuvant To Enhance Immune Effect Of This Vaccine

To develop safe and effective AIDS vaccine to control the spread of the humanimmunodeficiency virus (HIV) is one of the best ways to restraint the AIDS epidemic.Although there have been dozens of vaccines in clinical trials, but has not yet been avaccine proved effective protection to high-risk groups. To continue the new AIDSvaccine research and development is urgently needed. At the same time, to utilize avariety of vaccine adjuvants to enhance immune effect of HIV vaccine is a newstrategy in the present study.This study evaluated immunogenicity of adenoviral vectors vaccines expressingHIV-1Subtype B gp160. BALB/c mice were injected with Ad5-HIVgp160at dosageof2×106VP,2×107VP,2×108VP,2×109VP and2×1010VP. Specific cellular immuneresponse and humoral immune responses in immunized mice were detected by IFN-γELISPOT and ELISA. As the result, specific cellular immune response and humoralimmune response has been induced in each dose group mice,and the dose of2x108vp can inspire a high level of cellular and humoral immune responses in mice.Next, a synergistic effect of IL15gene adjuvants and poly(I:C) to enhanceimmunity effect of HIV-1B subtype gp160DNA and adenovirus vector vaccineexpressing HIV-1Subtype B gp160. First, the IL15DNA adjuvant pVR-IL15wasconstructed. And, BALB/c mice were injected with pVR-IL15and HIVgp160DNAprime/Ad5-HIVgp160boost alone or combined.Cellular and humoral immuneresponses and lymphocyte proliferative reaction were detected by IFN-γ ELISPOT,ELISA and CCK-8methods. The results show compared mice immunized vaccinealone, specific cellular and humoral immune response and the proliferative responsesof lymphocytes are obviously increased in mice combined immunization of pVR-IL15and HIVgp160DNA, Ad5vector vaccine. Next, pVR-IL15and poly(I:C) alone orcombined with HIVgp160DNA prime/Ad5-HIVgp160boost immunized BALB/cmice. And, cellular immune responses and lymphocyte proliferative reaction in micewere also measured by this methods. The results show that specific cellular responsesand lymphocyte proliferation in mice injected with pVR-IL15and poly(I:C) weresignificantly higher than using pVR-IL15alone. Further experiments demonstrate thatmice injected pVR-IL15combined with poly(I:C) in3days after immunization caninduce higher levels of specific cellular immune response than other groups of mice,and the trend of increasing can be extended to8weeks after immunization. Fluorescence quantitative PCR experiments further shows that in pVR-L15combinedwith poly(I:C) group, expression of Th1cytokines IFN-γ and anti-apoptotic factorsBcl-2were higher than other groups, and specific cellular immune responses andlymphocyte proliferation reaction intensity is certainly correlated with the Bcl-2expression.To sum up, the Ad5-HIVgp160vaccine can induce specific cellular immuneresponse and humoral immune response, and has the potential to be therapeuticeffective AIDS vaccine.IL15gene adjuvants combined with poly(I:C) can enhanceHIV DNA vaccine prime/adenovirus vaccine boost strategy, prolong the acting time.So the body’s immune response provides experimental support to IL15adjuvantscombined with poly(I:C) in clinical application.