可诱导广谱中和抗体的HIV膜蛋白基因变异模式研究

广谱中和抗体（BNAb）能够阻断HIV的感染，如何诱导其产生是艾滋病疫苗研发的关键。研究显示，BNAb的产生过程是抗体和病毒膜蛋白共进化的结果，膜蛋白诱导祖先抗体产生，在抗体的免疫压力下又发生变异，部分变异膜蛋白再次刺激和筛选B细胞，促进抗体成熟。可以看出，诱导抗体产生的初始病毒膜蛋白和促进抗体成熟的病毒中间体膜蛋白对于诱导机体产生具有广谱中和活性的抗体至关重要。在本研究中，我们拟以体内具有和不具有BNAb的HIV感染者为研究对象，通过病例对照研究分析两组人群感染的初始病毒膜蛋白基因差异，鉴定能够诱导BNAb产生的初始病毒膜蛋白特征性位点；通过回顾性队列研究，分析具有BNAb的感染者感染后系列样本病毒膜蛋白基因差异，筛选出能够促进中和抗体成熟、增加抗体中和滴度和广谱性的关键性变异，确定可诱导BNAb产生的HIV膜蛋白变异模式，为我国研究可诱导BNAb的艾滋病疫苗提供基础信息。

Broadly neutralizing antibody (BNAb) has been proved to be able to block HIVinfection. How to induce BNAb become the important point for HIV vaccines studies.Much data has shown that the produce of BNAb in vivo was the result ofco-evolution of HIV envelope and human antibodies. Antibodies were induced byenvelope protein and further put viral proteins unders immunal pressure. Thepressure pushes HIV env gene to mutate to escape human immunal pressure. As theresult, mutated HIV envelope protein promote the maturation of human antibodies.It can be seen that the unmutated original viral envelope protein and mutatedenveope proteins which could promote antibody matureation were important forinduction of BNAb. In this study, we want to enroll HIV-inected individuals whoobtained natural BNAb in vivo. The case-control study will be fulfilled to compareoriginal viral envelope gene from both case and control populations, the signaturesites important for inducing BNAb will be obtained. Furthermore, individuals whonatually obtained BNAb will be selected for retrospective cohort study. All ofserial samples from time when they were infected to when they obtained BNAb willbe used to anlyze envelope gene of HIV. The important mutations which couldpromote antibodies' evolution and enhance antibodies' neutralizing titer andbreadth will be screened. Finally, all of data will be pooled together to concludethe mutation patter of HIV envelope protein which can induce BNAb. The resultswill provide information for design of HIV vaccine which can induce BNAb.