HIV Specific Immunity in Highly Exposed Uninfected Women

高度暴露的未感染女性的 HIV 特异性免疫

• 批准号: 7694226
• 负责人: RICHARD M NOVAK
• 金额: $ 33.89万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7694226
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Adsorption; Antibodies; Antibody Formation; Antigens; Bacterial Infections; Binding; Biological Assay; Cervical; Cohort Studies; Collaborations; Country; Data; Disease Progression; Environment; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Focal Infection; Frequencies; Future; Genital system; Geographic Locations; Goals; HIV; HIV Infections; HIV Seropositivity; Heterosexuals; Humoral Immunities; Immune response; Immunity; Immunoglobulin A; Immunoglobulin G; Individual; Infection; Instruction; Knowledge; Liquid substance; Measures; Mediating; Modeling; Monoclonal Antibodies; Mucosal Immunity; Multiple Partners; Participant; Pathogenesis; Peptides; Persons; Play; Predisposition; Principal Investigator; RNA; Recruitment Activity; Research; Risk; Risk Behaviors; Role; Rwanda; Sampling; Serum; Specificity; Time; Tissues; Viral; Viral Load result; Virus; Visit; Woman; acquired immunity; antibody-dependent cell cytotoxicity; base; cohort; cytokine; genital secretion; gp160; high risk; insight; neutralizing antibody; neutralizing monoclonal antibodies; prevent; programs; response; transmission process; vaccine development

instructions): Women from different countries who are at high-risk of HIV infection through sexual contact may be protected from infection as a result of acquired immunity to the virus. Several studies demonstrate an HIV- specific humoral immune response in the genital tract of highly exposed, uninfected women. Our hypothesis is that the local immune response in the genital tract in highly exposed seronegative (ESN) women confers protection from infection with HIV. A better understanding of this potentially protective antibody response may provide insight into the role mucosal immunity plays in preventing HIV infection and may help inform Future research related to HIV prevention in women. This goal of this project is to characterize the HIV- specific antibody response in the genital tracts of ESN women from the US and to compare their responses to those of HIV infected elite suppressors and progressors from the Women's Interagency HIV Study (WIHS). We will determine whether the local genital antibody response is more broadly reactive in women who have been repeatedly exposed vaginally but remain uninfected. Preliminary data demonstrate that low concentrations of antibody against HIV are present in the genital fluids of more than 60% of the women in our cohort, many with reactivity against more than one pseudotype of virus. We will (1) characterize local genital tract binding and neutralizing antibodies in our cohort of high risk, seronegative women, including characterization of neutralizing antibodies that bind to broadly neutralizing epitopes (2) evaluate the durability of antibodies in the genital tract including ADCC, ADCVI and cross clade ADCC activity, (3) compare the specificity and frequency of antibodies in the genital tract of ESN women with HIV infected progressors and elite suppressors from the WIHS cohort, and (4) compare the humoral immune response in the genital tract of ESN women from Rwanda with those of ESN women from the US. It would be extremely valuable to know the particular components of the genital immune response that protect against heterosexual transmission of HIV. This knowledge could be used to develop a vaccine that effectively and selectively stimulates protective local immunity in the female genital tract against HIV infection. RELEVANCE (See instructions): Exposed seronegative women (ESN) with heterosexual exposure from multiple partners have antibodies in their genital tract against HIV. We will characterize their response and compare it to that of women who were infected following exposure. If these studies reveal differences in the types of antibodies produced by these women, it could help us understand the type of antibody needed for protection against HIV infection.

指示）： 来自不同国家的女性通过性接触感染艾滋病毒的风险可能很高 由于获得了对病毒的免疫力，从而免受感染。多项研究表明，HIV- 高度暴露、未感染的女性生殖道中的特异性体液免疫反应。我们的假设 高度暴露的血清阴性（ESN）女性生殖道的局部免疫反应赋予 防止感染艾滋病毒。更好地了解这种潜在的保护性抗体反应 可能有助于深入了解粘膜免疫在预防艾滋病毒感染中的作用，并可能有助于提供信息 与女性艾滋病毒预防相关的未来研究。该项目的目标是描述艾滋病毒的特征 美国 ESN 女性生殖道中的特异性抗体反应并比较她们的反应 来自妇女机构间艾滋病毒研究的艾滋病毒感染精英抑制者和进展者 （WIHS）。我们将确定局部生殖器抗体反应是否在女性中具有更广泛的反应性 多次接触阴道但未感染的人。初步数据表明，低 超过 60% 的女性的生殖器液中存在一定浓度的 HIV 抗体 我们的队列中，许多人对不止一种假型病毒有反应。我们将 (1) 描述当地的特征 在我们的高风险、血清阴性女性队列中，生殖道结合和中和抗体，包括 与广泛中和表位结合的中和抗体的表征 (2) 生殖道中抗体的持久性，包括 ADCC、ADCVI 和跨进化枝 ADCC 活性，(3) 比较感染 HIV 的 ESN 女性生殖道中抗体的特异性和频率 WIHS 队列中的进展者和精英抑制者，以及（4）比较 来自卢旺达的 ESN 妇女和来自美国的 ESN 妇女的生殖道。这将是非常 了解生殖器免疫反应的特定组成部分很有价值，这些部分可以预防 艾滋病毒的异性传播。这些知识可用于开发一种有效且有效的疫苗 选择性刺激女性生殖道的保护性局部免疫力，抵抗艾滋病毒感染。 相关性（参见说明）： 与多个伴侣接触过的异性恋女性（ESN）体内有抗体 他们的生殖道抵抗艾滋病毒。我们将描述她们的反应，并将其与接受治疗的女性的反应进行比较。 接触后感染。如果这些研究揭示了这些抗体产生的抗体类型的差异 对于女性来说，它可以帮助我们了解预防艾滋病毒感染所需的抗体类型。