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

一种有效的艾滋病毒疫苗需要激发有效的体液和细胞免疫反应，才能真正 消毒免疫力。HIV特异性的CD4T细胞反应，特别是增殖性反应，是一种有效的 与病毒血症的控制相关，但在艾滋病毒感染者中相对罕见且程度较低。 HIV感染者的自体中和抗体通常效价低，缺乏足够的 广度，以中和异源病毒。我们目前的候选艾滋病毒疫苗目前正在接受测试 人类能够引发CD8细胞免疫反应，并很可能对 感染，但不太可能产生中和抗体。该HIVRAD计划项目将识别病毒 在病毒血症控制程度不同的受试者中诱发广泛中和抗体的序列。 这个特殊的项目(项目2)将利用我们对早期的大量研究对象的访问 和慢性艾滋病毒感染，其中包含几个人在没有病毒血症的情况下控制了病毒血症 抗逆转录病毒疗法。从多年来研究细胞免疫反应的专业知识和我们初步的 数据，我们知道其中几个人有完整的病毒特异性CD4T细胞反应。我们的目标是 该项目旨在确定CD4T细胞和B细胞之间的相互作用，以预测艾滋病毒感染的能力 个体产生广泛的中和抗体。我们还设计了新技术，使 美国将对HIV包膜特异的B细胞进行分类，我们将用它从患有艾滋病的患者中分离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帮手图景 维持B细胞反应所需的功能，评估慢性感染患者CD4-B细胞功能的分析 和接种疫苗的个体，以及将被用来进一步表征艾滋病毒的新抗体试剂 中和活性。 相关性(请参阅说明)： 了解允许产生广谱中和抗体的因素对疫苗至关重要。 发展。在这个项目中，我们将探索T细胞和B细胞之间完整的相互作用的假设 对于发展和维持艾滋病毒感染者的广谱中和抗体至关重要。

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.