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）： 来自不同国家的妇女通过性接触处高风险的艾滋病毒感染可能是 获得了对病毒的免疫力，因此免受感染的保护。几项研究证明了HIV- 高度暴露的未感染妇女的生殖道中的特定体液免疫反应。我们的假设 是在高度暴露的血清神经（ESN）妇女同意的生殖道中的局部免疫反应 防止感染艾滋病毒。更好地理解这种潜在的保护抗体反应 可能会洞悉粘膜免疫在预防艾滋病毒感染中的作用，并可能有助于告知 与女性预防HIV有关的未来研究。该项目的这个目标是表征HIV- 来自美国ESN妇女生殖道中的特定抗体反应并比较其反应 艾滋病毒感染妇女艾滋病毒艾滋病毒研究 （wihs）。我们将确定局部生殖器抗体反应在女性中是否具有更广泛的反应性 他们曾多次阴道暴露但未感染。初步数据表明低 在超过60％的女性的生殖器流体中存在抗HIV抗体的浓度 我们的队列，许多对多种病毒假型的反应性。我们将（1）特征本地 在我们的高风险同类中，生殖道结合和中和抗体，包括血清神经妇女，包括 与广泛中和表位结合的中和抗体的表征（2）评估 生殖道中抗体的耐用性，包括ADCC，ADCVI和Cross Crade 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 从WIHS队列中的进步者和精英抑制器，（4）比较中的体液免疫反应 来自卢旺达的ESN妇女的生殖道与来自美国的ESN妇女的生殖道。这将是极其 知道保护防止生殖器免疫反应的特定组成部分很有价值 艾滋病毒的异性传播。这些知识可用于开发有效的疫苗 有选择地刺激女性生殖道抗HIV感染的保护性局部免疫。 相关性（请参阅说明）： 来自多个伴侣的异性恋暴露的裸露的血清神经女性（ESN）具有抗体 他们对艾滋病毒的生殖道。我们将表征她们的回应，并将其与妇女的反应进行比较 受感染后的暴露。如果这些研究揭示了这些研究产生的抗体类型的差异 妇女，它可以帮助我们了解保护艾滋病毒感染所需的抗体类型。