Defining Immune Deficits in HIV-1 Infected Women

定义 HIV-1 感染女性的免疫缺陷

• 批准号: 7766258
• 负责人: Catherine A Blish
• 金额: $ 12.37万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766258
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Agreement; Antibody Formation; Antigens; CD4 Positive T Lymphocytes; CD8B1 gene; Cell division; Cellular Immunity; Chronic; Cryopreserved Cell; Cytolysis; Epidemic; Failure; Flow Cytometry; Future; Goals; HIV; HIV-1; High Risk Woman; Immune; Immune response; Immunity; Individual; Infection; Kenya; Length; Mediating; Methods; Peripheral Blood Mononuclear Cell; Play; Production; Reporting; Research Personnel; Resistance; Role; Sampling; Specificity; Staining method; Stains; T-Cell Proliferation; T-Lymphocyte; Vaccine Design; Vaccines; Variant; Viral; Virus; Woman; cohort; cytokine; insight; neutralizing antibody; pandemic disease; prevent; programs; research study; response; superinfection

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.

艾滋病大流行仍未受到检查，有效的疫苗的前景可提供最大的希望 预防艾滋病毒。我们仍在为开发保护性疫苗的努力受到了我们仍然的事实的阻碍 不了解与HIV-1的免疫相关性。正在进行的疫苗试验有望提供有关 在慢性感染过程中控制HIV-1复制的免疫反应是否可以 还可以在介导HIV-1的新感染保护中发挥作用。 HIV-1的最新报告 超级感染（也称为重新感染，被定义为第一种病毒后第二个病毒感染 在个人中建立），建议在自然感染期间产生的免疫反应不 一定会诱发保护性免疫。因此，鉴定在近代染料中的潜在免疫缺陷 个人对于疫苗设计很重要。我们的实验室最近确定了几例HIV-1病例 肯尼亚蒙巴萨的一批高风险女性中的超级感染。我们假设在 对HIV-1的体液和细胞免疫都有助于第二个病毒菌株建立 感染。该提议的目的是表征对HIV-1的体液和细胞免疫反应 在超级感染的个体中，并将​​这些回应与尚未成为的妇女的回应进行比较 超级感染。为了分析体液免疫反应，我们将首先生成一个全长的面板， 最初感染和超级感染菌株的功能包膜克隆。我们将使用这些信封 开发一系列病毒，我们可以评估中和的效力和广度 超级感染妇女和未显示超级感染证据的妇女的抗体反应。我们 旨在使用多参数流细胞术和多重细胞因子来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。 我们将评估细胞因子产生，细胞解和增生性的缺陷或变化 在超级感染的女性中，CD4+和CD8+ T细胞之间的容量。分析体液和细胞 已成为超级感染的妇女的免疫反应将有助于确定两者的相关性 保护和失败的艾滋病毒免疫力；这样的进步将提供关键的见解，以纳入未来 疫苗设计。