Study On Immune Strategy Of Vector-based Therapeautic Vaccines Expressing SIV And HIV Genes With Adjuvants

AIDS has been pandemic for over 30 years worldwide, yet there is no method able to thoroughly remove virus infection and cure the disease.The main goal of the therapeutic HIV vaccine is to reconstruct or elicit infected people’s own anti-HIV immune function, enhance the strength of those people’s HIV specific immune response, reduce viral load, delay the time of people living with HIV develop into AIDS patients and ultimately achieve functional cure of patients.Thus, therapeutic HIV vaccine is considered to be a potentially promising AIDS therapy. SIV and HIV-1are highly homologous and have similar pathological process and immune response after infected the host. Due to the lack of an effective HIV vaccine animal model,SIV/monkey model can effectively evaluate the efficacy of the HIV vaccine.There are many researches about rAd5 HIV vaccine, yet,due to the high infection rate of Ad5,other serotype adenoviral vectors or chimeric viruses begin to be studied. In recent years, many researches are focused on the strategy of using adjuvants to enhance immune effect of AIDS vaccine.This study constructed recombinant adenoviral vector vaccine expression SIV gag gene(rAd5F35-SIV gag) by using AdEasyTM adenovirus packaging system. The identification of rAd5F35-SIV gag showed that it contained SIV gag gene and could express gag protein effectively. Then we studied the pharmacodynamics of the vaccine in mice. BALB/c mice were injected with Ad5F35-SIV gag vaccine at different doses. Specific cellular immune response in immunized mice were detected by ELISPOT. The result showed specific cellular immune response has been induced in each dose group mice and the dose of 1×108 TCID50 can inspire a high level of cellular immune responses in mice.Previous studies indicated that the strategy of sequential and repeated immunization with vector-based AIDS vaccines could induce high level and long-lasting HIV-specific cellular immune responses in mice and rhesus macaques.BALB/c mice were injected with Ad5F35-SIV gag, combined with our previous constructed pVR-SIV gag(DNA vaccine) and Ad5-SIV gag vaccine. The strategy of DNA prime/Ad5F35-SIV gag boost, then re-boost with Ad5-SIV gag vaccine elicited stronger Gag-specific cellular immune response.This study constructed mouse interleukin 7 DNA adjuvant(pVR-IL7) and mouse interleukin 21 DNA adjuvant(pVR-IL21).To study the immune effects of IL-7, IL-21 as gene adjuvants, Poly(I:C) and CpG ODN for HIV vaccine, BALB/c mice receivedDNA prime-adenoviral vector boost immunization with pVR-HIVenv-Ad5-HIVenv alone or combined with pVR-IL7,pVR-IL21, Poly(I:C) and CpG ODN. Cellular and humoral immune response were assessed by IFN-γ enzyme-linked immunosorbent spot assay and enzyme-linked immunosorbent assay.Compared with those immunized with vaccines alone, the mice immunized with pVR-IL7 had increased specific cellular response, CpG ODN had synergic effects with IL7 as adjuvantsIL7 but not IL21 can enhance the specific cellular immune response of Ad5-HIVenv in mice.