Characterization of T & B cell responses correlated with broad neutralizing Abs

有效的艾滋病毒疫苗需要引起有效的体液和细胞免疫反应， 消除免疫力HIV特异性CD 4 + T细胞反应，特别是增殖反应，是一种有效的免疫调节剂。 与病毒血症的控制相关，但在艾滋病毒感染者中相对不常见且程度较低。 HIV感染受试者中的自体中和抗体通常是低滴度的，并且缺乏足够的免疫原性。 以中和异源病毒。我们目前的艾滋病毒候选疫苗目前正在测试中， 人类能够引发CD 8+细胞免疫应答，并且可以很好地提供部分保护， 感染，但不太可能产生中和抗体。这个HIVRAD计划项目将识别病毒 在具有不同程度的病毒血症控制的受试者中引发广泛中和抗体的序列。 这个特殊的项目（项目2）将利用我们对大量早期受试者的访问， 和慢性艾滋病毒感染，其中包含几个人与病毒血症的控制，在没有 抗逆转录病毒疗法从多年的专业知识研究细胞免疫反应，并从我们的初步 根据数据，我们知道这些个体中有几个人具有完整的病毒特异性CD 4 + T细胞应答。我们的目标 该项目旨在确定CD 4 + T细胞和B细胞之间的相互作用，以预测HIV感染者的能力。 个体产生广泛中和抗体。我们还设计了新技术 我们将对HIV包膜特异性的B细胞进行分类，我们将使用这些细胞从患有HIV包膜的受试者中分离B细胞克隆。 广泛中和抗体活性。这个项目的结果将是一个全面的图片助手 维持B细胞应答所需的功能，评估慢性感染中CD 4-B细胞功能的测定 和接种疫苗的个人，以及将用于进一步表征艾滋病毒的新抗体试剂 中和活性 相关性（参见说明）： 了解能够产生广泛中和抗体的因素对疫苗至关重要 发展在这个项目中，我们将探讨的假设，完整的相互作用之间的T细胞和B细胞 对HIV感染者体内广泛中和抗体的产生和维持至关重要。

An effective HIV vaccine will need to elicit potent humoral and cellular immune responses for true sterilizing immunity. HIV-specific CD4 + T cell responses, particularly proliferative responses, are a potent correlate of control of viremia, but relatively uncommon and of low magnitude in HIV infected individuals. Autologous neutralizing antibodies in HIV infected subjects are typically of low titer, and lack sufficient breadth to neutralize heterologous viruses. Our current HIV vaccine candidates currently under testing in humans are able to elicit CD8+ cellular immune responses, and may well provide partial protection against infection, but are unlikely to generate neutralizing antibodies. This HIVRAD program project will identify viral sequences that elicit broadly neutralizing antibodies in subjects with varying degrees of control of viremia. This particular project (project 2) will take advantage of our access to a large cohort of subjects with early and chronic HIV infection, and which contains several individuals with control of viremia in the absence of anti-retroviral therapy. From years of expertise studying cellular immune responses, and from our preliminary data, we know several of these individuals have intact virus-specific CD4+ T cell responses. Our goalwith this project is to identify interactions between CD4+ T cells and B cells that predict the ability of HIV-infected individuals to generate broadly neutralizing antibodies. We have also designed new technology that allows us to sort B cells specific for HIV envelope, which we will use to isolate B cell clones from subjects with broadly neutralizing antibody activity. The outcome of this project will be a comprehensive picture of helper function required to maintain B cell responses, assays to assess CD4-B cell function in chronically infected and vaccinated individuals, and new antibody reagents that will be used to further characterize HIV neutralizing activity. RELEVANCE (See instructions): Understanding the factors that allow the generation of broadly neutralizing antibodies is critical to vaccine development. In this project we will explore the hypothesis that intact interactions between T cells and B cells is critical to the development and maintenance of broadly neutralizing antibodies in HIV-infected individuals.