Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

描述(由申请人提供)：CHAVI-ID申请的中心假设是，一种成功的艾滋病毒疫苗应该引起保护性抗体(Abbs)，B细胞和CD4+T细胞反应的组合对于疫苗保护的诱导和长期维持至关重要。该应用程序的总体任务是定义免疫原和免疫方案，在临床前模型中诱导持续的HIV交叉保护B细胞和CD4+T细胞反应，从而指导预防性人类艾滋病疫苗的产品开发战略。我们建议通过两个重点和高度整合的努力，在深入了解免疫反应的关键属性的基础上开发一种艾滋病毒疫苗，这些免疫反应提供对艾滋病病毒的保护。焦点1将集中在B细胞和抗体研究上，以指导在适当的动物模型中产生保护性艾滋病毒抗体反应的免疫原的开发。Focus#2将专注于CD4+T细胞的研究，利用关键的初步数据，最大限度地利用T细胞通过免疫为B细胞反应提供的帮助，并利用CD4+T细胞的直接抗病毒活性。我们认为这种结合的方法将导致新的免疫原和免疫策略的发现，这些免疫原和免疫策略将产生可测量的交叉保护抗体反应。然后，我们将在这些进展的基础上反复改进最有希望的结构和方案，直到实现疫苗保护。我们建议的一个关键组成部分是我们在免疫学、病毒学和结构生物学方面的研究团队的实力。主任丹尼斯·伯顿在了解广泛的艾滋病毒抗体中和作用以及在艾滋病毒感染动物模型中的抗体保护方面做出了重大贡献。科学领导小组(SLG)的成员是拉蒂·艾哈迈德、米歇尔·努森茨韦格、布鲁斯·沃克和伊恩·威尔逊，他们在描述抗艾滋病毒抗体的结构和功能以及诱导和维持对病毒的B和T细胞免疫方面取得了重要进展。该团队将由五个科学研究支持部门(SRSC)支持，其中包括强大的运营和管理部门，这些部门已经组装在一起，最大限度地加快了实现指定目标的进展。

DESCRIPTION (provided by applicant): The central hypotheses of this CHAVI-ID application are that a successful HIV vaccine should elicit protective antibodies (Abs), and that the combination of B cell and CD4+ T ceil responses is critical for the induction and long-term maintenance of vaccine protection. The overall mission of the application is to define immunogens and immunization regimens that induce sustained HIV cross-protective B cell and CD4+ T cell responses in preclinical models and, thereby, guide product development strategies for a preventive human AIDS vaccine. We propose to develop an HIV vaccine based on a deep understanding of the critical attributes of immune responses that provide protection against AIDS viruses, through two focused and highly integrated efforts. Focus #1 will concentrate on B cell and antibody research to guide the development of immunogens that elicit protective HIV antibody responses in appropriate animal models. Focus #2 will concentrate on CD4+ T cell research, taking advantage of key preliminary data to maximize the T cell help offered to B cell responses through immunization, and to harness the direct antiviral activity of CD4+ T cells. We argue that this combined approach will lead to the discovery of novel immunogens and immunization strategies that will generate measurable cross-protective antibody responses. We will then build on such advances iteratively, by improving the most promising constructs and protocols until vaccine protection is achieved. A critical component of our proposal is the strength of our research team in immunology, virology and structural biology. The Director, Dennis Burton, has made major contributions to understanding broad antibody neutralization of HIV and antibody protection in animal models of HIV infection. The Scientific Leadership Group (SLG) members are Rati Ahmed, Michel Nussenzweig, Bruce Walker and Ian Wilson, who have made crucial advances in describing the structure and function of antibodies against HIV and the induction and maintenance of B and T cell immunity to the virus. The team will be sustained by five Scientific Research Support Components (SRSCs), including strong Operations and Management, that have been assembled to maximally accelerate progress toward the designated goals.