AIDS是严重危害人类健康的传染病，目前尚无有效疫苗可用。临床试验表明，Ad5病毒载体HIV疫苗会增强HIV感染；而ALVAC病毒载体疫苗却具有31.2%的有效性。申请人之前发现相比Ad5，ALVAC会活化炎性小体。随后炎性小体活化被证实与ALVAC载体疫苗的有效性相关。研究表明HIV最早通过感染肠道CD4+TRM来建立全身感染。我们前期发现ALVAC会降低介导CD4+T细胞进入肠道组织的归巢受体α4β7表达，从而可能减少肠道CD4+TRM产生而抑制HIV感染。本项目拟在前期研究基础上利用小鼠模型和本学科组建立的HIV感染北平顶猴模型研究：1)ALVAC是否通过活化炎性小体下调α4β7来抑制肠道CD4+TRM的产生；2)不同疫苗病毒载体对肠道CD4+TRM分布的影响；3)肠道CD4+TRM数量与HIV体内感染之间的关系。该研究将为HIV疫苗设计以及HIV防治提供重要的科学依据和理论支持。

AIDS is an infectious disease that seriously harms human health, but to date no efficacious vaccines are available. HIV vaccine efficacy clinical trials suggest that Ad5 viral vectored vaccines can increase HIV infection, while ALVAC viral vectored vaccines showed a 31.2% vaccine efficacy. Our previous study suggested that ALVAC can activate inflammasomes compared to Ad5. Following our finding, it is demonstrated the correlation of inflammasome activation and ALVAC vectored vaccine efficacy. Studies implied that the initial target cells of HIV infection is gut-resident CD4+ memory T cells (CD4+ TRM) and then HIV-infected gut CD4+ TRM promote systemic infection. Our preliminary data showed that compared with Ad5, ALVAC significantly down-regulated α4β7 protein, an homing receptor which mediates CD4 T cells entry into gut tissues. In this project, we plan to use mouse model and HIV-infected northern pig-tailed macaque model we established to study 1) whether ALVAC decreases α4β7 expression and then the generation of gut CD4+ TRM through activating inflammasomes; 2) the effect of different vaccine viral vectors on the distribution of gut CD4+ TRM; 3) the relationship of gut CD4+ TRM with HIV systemic infection. Our study will provide a scientific basis and theoretical support for HIV vaccine design and HIV prevention.