Protective immunity in HIV Highly exposed but uninfected subjects

描述(由申请人提供)：这是一种新的R21应用程序，用于研究暴露于HIV-1但未感染HIV-1的个人的潜在保护性免疫反应。在我们的初步数据中，我们已经表明，在大部分暴露于HIV-1但未感染HIV-1(暴露的血清阴性，ESN)的人中，检测到抗HIV-1蛋白水解酶和抗长末端散布核元件(LINE)特异性免疫反应。我们推测，接触HIV-1和HIV-1感染的细胞产品导致了这些反应，它们可能对防止HIV-1感染的建立负有部分责任。该基金提出了两个具体目标，以确定HIV-1蛋白酶识别的表位的特征，以及在使用一系列不同病毒的初级分离株的病毒抑制试验中，确定抗HIV-1蛋白酶和LINE特异性T细胞克隆在体外识别HIV-1感染细胞和抑制HIV-1病毒复制的有效性。这笔赠款产生的数据将为未来的R01提供初步数据，以便纵向跟踪一大批eSNs，以确定拥有这种免疫力是否与预防艾滋病毒-1传播有关。 公共卫生相关性：这是一种新的R21应用程序，用于研究暴露于HIV-1但未感染HIV-1的个人的潜在保护性免疫反应。

DESCRIPTION (provided by applicant): This is a new R21 application to investigate potentially protective immune responses in individuals exposed to HIV-1 but who are HIV-1 uninfected. In our preliminary data, we have shown that anti-HIV-1 protease and anti-long-terminal interspersed nuclear elements (LINE) specific immune responses are detected in a large fraction of individuals exposed to HIV-1, but who are HIV-1 uninfected (exposed seronegatives, ESN). We hypothesize that exposure to HIV-1 and HIV-1 infected cell products have led to these responses, and that they may be partially responsible for prevention of establishment of an HIV-1 infection. The grant proposes in two specific aims to characterize the epitopes recognized by HIV-1 protease and LINE specific T cells in HIV-1 exposed uninfected subjects, and to determine the efficacy of anti-HIV-1 protease and LINE specific T cell clones to recognize HIV-1 infected cells in vitro and to suppress HIV-1 viral replication in a viral inhibition assay using primary isolates of a range of different viruses. The data generated from this grant would provide preliminary data for a future R01 to longitudinally follow a large cohort of ESNs to determine whether possession of such immunity was associated with protection from HIV-1 transmission. PUBLIC HEALTH RELEVANCE: This is a new R21 application to investigate potentially protective immune responses in individuals exposed to HIV-1, but who are HIV-1 uninfected.