Immune responses to HIV virus immunization - Project 2

暴露前预防和治疗可以降低艾滋病毒感染率，但仍有近200万新感染者 每年都在全球范围内发生。一种能够引发针对艾滋病毒感染的长期保护性免疫的疫苗， 终结艾滋病流行的最佳前景。虽然没有获得许可的艾滋病毒疫苗， 在RV 144泰国试验中观察到的新发现为研制预防性疫苗带来了希望。为了改善这种功效， 深入了解疫苗保护的基本免疫机制至关重要。我们提出的 这些研究旨在产生关于如何提高抗HIV T细胞功能，诱导增强免疫功能， 效力和持久性，并开发引发广泛中和抗体的途径。我们处于一个独特的位置， 通过获得来自几个艾滋病毒疫苗试验的一组特殊样本来解决这些问题， 艾滋病毒感染队列的特征。我们建议的研究包括评估疫苗的动力学- 在相关解剖区室（淋巴结、骨髓和肠道）中诱导免疫应答， 访问尖端的分析方法，以生成非常适合我们提出的链接数据集， 综合系统生物学方法。我们的项目团队非常适合进行这些研究，因为 领导者和知名合作者专注于HIV疫苗研究，转化免疫学， 系统方法来理解免疫记忆和免疫相关分析。我们预计 我们的工作将揭示可检验的假设的基本机制之间的相互作用的关键组成部分， 先天性和适应性免疫反应，负责通过接种疫苗预防艾滋病毒。

Pre-exposure prophylaxis and treatment can lower HIV infection rates but nearly two million new infections still occur worldwide each year. A vaccine that can elicit long-lived protective immunity against HIV infection offers the best prospect to end the AIDS epidemic. While no licensed HIV vaccine is available, the modest efficacy observed in the RV144 Thai Trial raises hope that a preventive vaccine is possible. To improve on this efficacy, a deeper understanding of the underlying immune mechanism of vaccine protection is crucial. Our proposed studies aim at generating critical insights on how to improve anti-HIV T cell function, induce enhanced immune potency and durability, and develop paths to elicit broad neutralizing antibodies. We are in a unique position to address these topics with access to an exceptional set of samples from several HIV vaccine trials and well- characterized HIV infection cohorts. Our proposed studies include assessment of the kinetics of the vaccine- induced immune response in relevant anatomic compartments (lymph nodes, bone marrow and gut) and access to cutting edge analytical methods to generate linked datasets that are ideally suited for our proposed, comprehensive systems biology approach. Our project team is uniquely suited to conduct these studies, as leaders and well-established collaborators focused on HIV vaccine research, translational immunology, systems approaches to understand immunological memory, and immune correlates analyses. We expect that our work will reveal testable hypotheses on the underlying mechanistic interplay between key components of the innate and adaptive immune response that are responsible for protection against HIV by vaccination.