Defining Immune Deficits in HIV-1 Infected Women

定义 HIV-1 感染女性的免疫缺陷

• 批准号: 7192411
• 负责人: Catherine A Blish
• 金额: $ 11.29万
• 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/7192411
• 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：艾滋病大流行仍未受到检查，有效疫苗的前景为预防艾滋病毒提供了最大的希望。我们仍然不了解与HIV-1的免疫相关的事实，我们为开发保护性疫苗的努力受到了阻碍。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也可以在介导HIV-1新感染的保护中发挥作用。 HIV-1近代感染的​​最新报道（也称为重新感染，被定义为第一种病毒在个体中已经建立后第二种病毒的感染），这表明自然感染期间产生的免疫反应没有 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。该提案的目的是表征超级感染个体中对HIV-1的体液和细胞免疫反应，并将这些反应与尚未被超级感染的女性的反应进行比较。为了分析体液免疫反应，我们将首先生成一个最初感染和超级感染菌株的全长，功能性封底克隆。我们将使用这些信封来开发一系列病毒，并可以评估超级感染妇女中中和抗体反应的效力和广度，而在不显示超级感染证据的妇女中。我们的目的是使用多参数流式细胞术和多路复用细胞因子评估刺激外周血单核细胞用HIV-1和非HIV-1抗原刺激细胞免疫的相关性。我们将评估超级感染的女性中CD4+和CD8+ T细胞中细胞因子产生，细胞溶解和增生能力的缺陷或变化。对已接触的妇女的体液和细胞免疫反应的分析将有助于确定保护性和失败的HIV免疫的相关性；这样的进步将提供关键的见解，以纳入未来的疫苗设计。