HIV Specific Immunity in Highly Exposed Uninfected Women

说明）： 来自不同国家的通过性接触感染艾滋病毒的高风险妇女可能 由于对病毒的获得性免疫而免受感染。几项研究表明，艾滋病毒- 高度暴露的未感染妇女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）妇女生殖道局部免疫反应， 保护免受艾滋病毒感染。更好地理解这种潜在的保护性抗体反应 可以提供深入了解粘膜免疫在预防HIV感染中的作用， 未来的研究与妇女艾滋病毒预防有关。该项目的目标是描述艾滋病毒- 美国ESN女性生殖道中的特异性抗体反应，并比较其反应 女性跨部门HIV研究中的HIV感染精英抑制者和进展者 （WIHS）。我们将确定是否局部生殖器抗体反应是更广泛的反应，在妇女 反复暴露于阴道但未被感染的人初步数据显示，低 2005年，60%以上的妇女生殖器液中存在高浓度的艾滋病毒抗体。 我们的队列中，许多人对一种以上的假型病毒具有反应性。我们将（1）描述本地 生殖道结合和中和抗体在我们的高风险队列，血清阴性妇女，包括 结合广泛中和表位的中和抗体的表征（2）评估 生殖道中抗体的持久性，包括ADCC、ADCVI和交叉进化枝ADCC活性，（3） 比较ESN女性HIV感染者生殖道中抗体的特异性和频率 来自WIHS队列的进展者和精英抑制者，以及（4）比较来自WIHS队列的进展者和精英抑制者的体液免疫应答。 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。是极其 了解生殖器免疫反应的特定成分是有价值的， 艾滋病毒的异性性传播。这些知识可以用来开发一种疫苗， 选择性地刺激女性生殖道中针对HIV感染的保护性局部免疫。 相关性（参见说明）： 暴露于多个伴侣的异性性接触的血清阴性女性（ESN）在以下人群中有抗体： 他们的生殖道抵抗艾滋病病毒。我们将描述他们的反应，并将其与那些 暴露后感染。如果这些研究揭示了这些人产生的抗体类型的差异 它可以帮助我们了解预防艾滋病毒感染所需的抗体类型。

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.