Defining Immune Deficits in HIV-1 Infected Women

艾滋病继续肆无忌惮，有效疫苗的前景提供了最大的希望 用于预防艾滋病毒。我们开发保护性疫苗的努力受到了阻碍，因为我们仍然 不了解HIV-1免疫的相关性。正在进行的疫苗试验有望提供对 在慢性感染期间参与控制HIV-1复制的免疫反应是否可以 在预防新感染艾滋病毒-1方面也起到了中介作用。关于HIV-1的最新报道 重叠感染(也称为再感染，定义为在第一个病毒已经存在后被第二个病毒感染 表明在自然感染期间产生的免疫反应不会 必然会引起保护性免疫。因此，识别重复感染的潜在免疫缺陷 个体将是疫苗设计的重要因素。我们的实验室最近发现了几例HIV-1病例 肯尼亚蒙巴萨一群高危妇女中的双重感染。我们假设美国的财政赤字 对HIV-1的体液免疫和细胞免疫都有助于第二种病毒株建立 感染。这项建议的目的是描述针对HIV-1的体液和细胞免疫反应。 并将这些反应与未成为 过度感染。为了分析体液免疫反应，我们首先要生成一个全长的面板， 最初感染和重复感染菌株的功能性包膜克隆。我们将用这些信封 开发一组病毒，我们可以用它来评估中和的效力和广度 双重感染妇女和未表现出双重感染证据的妇女的抗体反应。我们 目的应用多参数流式细胞术和多种细胞因子鉴定细胞免疫相关因素 HIV-1和非HIV-1抗原刺激外周血单核细胞后的评估。 我们将评估是否在细胞因子的产生、细胞溶解和增殖方面存在缺陷或改变 重叠感染妇女外周血中CD4和CD8T细胞的能力体液分析和细胞分析 双重感染的女性的免疫反应将有助于确定两者的相关性 对艾滋病毒的保护性免疫和失败的免疫；这些进展将提供关键的见解，以纳入未来 疫苗设计。

The AIDS pandemic continues unchecked, and the prospect of an effective vaccine provides the best hope for HIV prevention. Our efforts to develop a protective vaccine have been hampered by the fact that we still do not understand correlates of immunity to HIV-1. Ongoing vaccine trials promise to provide insight into whether the immune responses that are involved in controlling HIV-1 replication during chronic infection can also play a role in mediating protection from new infection with HIV-1. Recent reports of HIV-1 superinfection (also called re-infection, defined as infection by a second virus after the first virus is already established in the individual), suggest that the immune responses generated during natural infection do not necessarily induce protective immunity. Thus, identifying potential immune deficits in superinfected individuals will be important for vaccine design. Our lab has recently identified several cases of HIV-1 superinfection among a cohort of high-risk women in Mombasa, Kenya. We hypothesize that deficits in both humoral and cellular immunity to HIV-1 contribute to the ability of a second viral strain to establish infection. The aims of this proposal are to characterize the humoral and cellular immune responses to HIV-1 in superinfected individuals, and to compare these responses to those of women who have not become superinfected. To analyze the humoral immune responses, we will first generate a panel of full length, functional envelope clones from initially infecting and superinfecting strains. We will use these envelopes to develop a panel of viruses with which we can assess the potency and the breadth of the neutralizing antibody responses in superinfected women and in women who do not show evidence of superinfection. We aim to identify correlates of cellular immunity using multiparameter flow cytometry and multiplex cytokine assessment following stimulation of peripheral blood mononuclear cells with HIV-1 and non-HIV-1 antigens. We will assess whether there are deficits or changes in cytokine production, cytolysis, and proliferative capacity among CD4+ and CD8+ T cells in superinfected women. Analyses of the humoral and cellular immune responses of women who have become superinfected will aid in defining correlates of both protective and failed immunity to HIV; such advances will provide key insights to incorporate into future vaccine design.