抗艾滋病毒（HIV）广谱中和抗体（BnAbs）能阻止多种HIV病毒株感染，成为HIV疫苗研究的重要方向。但现有免疫原和疫苗策略尚无法诱导出高效的抗HIV BnAbs，提示更深入的抗体产生机制研究势在必行，这就需要理想的动物模型。前期，我们发现SHIV病毒感染恒河猴能自发产生抗HIV BnAbs反应，但存在抗体生成率低、生成时间长等问题。基于此，本研究拟从模型组织样品库筛选出抗HIV BnAbs阳性样品，使用病毒靶向测序和单拷贝PCR确定BnAbs启动Env基因，使用单个B细胞分析和免疫组库确定前体B细胞BCR信息；在此基础上，通过新型SHIV病毒构建和易感动物筛选，结合动物CD8+ T细胞耗竭技术，建立抗HIV BnAbs生成模型。本研究将继续探索恒河猴抗HIV BnAbs产生机制，成功建立抗HIV BnAbs生成模型，为HIV/AIDS的免疫原设计及疫苗策略探索提供重要信息和关键平台。

Even after over 30 years of intensive struggle, The spread of HIV/AIDS remains a serious public health problem in the world, including China. There is still no effective anti-HIV vaccine that is thought to be the only hope to prevent HIV epidemic. Recently, some anti-HIV broadly neutralizing antibodies (BnAbs) have been found from the HIV elite controller who are able to control viral load below 50 copies/ml of plasma without treatment. These antibodies have unique morphological structures and have been proved to be able to interrupt the infection of the HIV strains that have different genetic diversity in vitro and in vivo. So anti-HIV BnAbs has been considered an important opportunity for HIV vaccine development. However, the existing immunogens and vaccine strategies so far have not been able to elicit strong anti-HIV BnAbs, suggesting that further mechanism of antibody production is need to be uncover. So an ideal animal model has played a significant part in this. In our previous study, we found that SHIV virus-infected rhesus monkeys can spontaneously produce anti-HIV BnAbs, but it took a too long time for the antibodies production and maturation, and only a few of the infected animals can produce the antibodies. To solve the problems above, in this study, we will screen and obtain some anti-HIV BnAbs positive samples from our animal model sample bank using neutralization test. Then found the BnAbs-initiating Env from these positive samples using virus targeted sequencing and single genome amplification. And determine BCR of precursor B cells using single B cell analysis and immune repertoire. Base on that, a novel anti-HIV BnAbs production model will be established through the construction of a novel SHIV virus and screening of susceptible animals, combined with animal CD8+ T cell depletion techniques. This study will help us continue to explore the mechanism of anti-HIV BnAbs production in rhesus monkeys, and establish a novel animal model for anti-HIV BnAbs production and maturation successfully. It will provide important information and key platforms for HIV/AIDS immunogen design and vaccine strategy exploration.