Defining Immune Deficits in HIV-1 Infected Women

艾滋病的流行继续得不到控制，有效疫苗的前景提供了最好的希望 预防艾滋病。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深入了解 在慢性感染过程中参与控制HIV-1复制的免疫反应是否可以 还在介导保护免受新的HIV-1感染方面发挥作用。HIV-1的最新报道 重复感染（也称为再感染，定义为在第一种病毒已经感染后， 在个体中建立），表明在自然感染期间产生的免疫应答不 必然会产生保护性免疫。因此，确定潜在的免疫缺陷， 个体对于疫苗设计很重要。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， 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 感染该提案的目的是描述对HIV-1的体液和细胞免疫应答 并将这些反应与未感染的女性进行比较， 超级感染为了分析体液免疫应答，我们将首先生成一组全长， 来自初始感染和重复感染菌株的功能性包膜克隆。我们会用这些信封 开发一组病毒，我们可以评估中和的效力和广度， 在双重感染妇女和没有双重感染证据的妇女中的抗体反应。我们 目的利用多参数流式细胞术和多种细胞因子鉴定细胞免疫的相关性 用HIV-1和非HIV-1抗原刺激外周血单核细胞后的评估。 我们将评估是否有缺陷或变化，细胞因子的生产，细胞溶解，增殖， CD4+和CD8 + T细胞的能力。体液和细胞分析 双重感染妇女的免疫反应将有助于确定两者的相关性 保护和失败的免疫艾滋病毒;这些进展将提供关键的见解，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.