Female genital tract immunity and HIV vaccine responses

越来越多的证据表明，通过性接触感染艾滋病毒的高风险的不同地理位置的妇女可能会由于对该病毒的获得性免疫力而免受感染。几项研究现在已经证明，在高度暴露的未感染妇女的生殖道分泌物中存在艾滋病毒特异性的细胞和体液免疫反应。更好地了解这些潜在的保护性反应可能有助于艾滋病毒预防性疫苗的开发，并可能为在未来的疫苗试验中将生殖道作为预防艾滋病毒传播的免疫途径的可能用途提供洞察。这项提议有两个目的。第一个目标是描述和比较现有妇女队列中生殖道中艾滋病毒特异性体液和细胞反应的特征和比较。这项提议有两个目的。第一个目标是描述和比较现有女性队列中艾滋病毒特异性体液和细胞反应的特点和比较：Wish项目/疾控中心愿景研究中的未感染艾滋病毒的妇女，她们通过性传播高度暴露于艾滋病毒；COIP/NIDA针具交换研究中的33名未感染艾滋病毒的妇女(IDU)，她们父母有很高的接触机会，但性接触程度低；UIC医学中心妇科诊所的33名妇女感染艾滋病毒的风险很小或没有风险；以及芝加哥WIHS研究的33名艾滋病毒感染妇女。第二项研究的目的是测量参与艾滋病毒疫苗疗效试验的妇女生殖道中的艾滋病毒特异性体液和细胞反应。30名女性将从正在进行的VaxGen VAX0004疗效试验中招募，该试验正在Project Wish进行。Wish项目将从计划于2001年6月开始的NIAID HVTN 301疫苗试验中招募205名女性。CVL、宫颈取材、血清和风险评估将从参与这些粘膜免疫研究的所有女性中收集。细胞刷子将被用来收集子组妇女的宫颈细胞。将每隔六个月从参与AIM 1研究的妇女那里收集两个样本。AIM 2中疫苗研究的样本采集将与疫苗接种时间表一致。体液免疫的建议测量方法包括HIV特异性结合抗体、中和抗体和ADCC抗体。建议的细胞免疫测量包括CTL和CD4淋巴细胞增殖和趋化因子受体的表达。

A growing body of evidence suggests that geographically diverse women who are high risk of HIV infection through sexual contact may be protected from infection as a result of acquired immunity to the virus. Several studies have now demonstrated both HIV-specific cellular and humoral immune responses in the genital tract secretions of highly exposed, uninfected women. A better understanding of these potentially protective responses may aid in HIV preventive vaccine development, and may provide insight into the possible utility of targeting the genital tract as a route of immunization against HIV transmission in future vaccine trials. This proposal has two aims. The first aim is to characterize and compare HIV-specific humoral and cellular responses in the genital tract tracts of existing cohorts of women. This proposal has two aims. The first aim is to characterize and compare HIV-specific humoral and cellular responses in the genital tracts of existing cohorts of women: 64 uninfected women from the Project WISH/CDC Vision study who are highly exposed to HIV through sexual transmission; 33 uninfected women (IDUs) from the COIP/NIDA Needle Exchange study who have high parental exposure and low sexual exposure to HIV; 33 women have little or no risk of exposure to HIV from the UIC Medical Center GYN clinic; and, 33 HIV-infected women from the Chicago WIHS study. The second study aim is to measure the HIV-specific humoral and cellular responses in the genital tracts of the women in participating in HIV vaccine efficacy trials. Thirty women will be recruited from the ongoing VaxGen VAX0004 efficacy trials that are ongoing at Project WISH. Project WISH will recruit two hundred five women from the NIAID HVTN 301 vaccine trials that are scheduled to begin in June, 2001. CVLs, cervical wicks, serum, and risk assessments will be collected from all women participating in these mucosal immunity studies. A cytobrush will be used to collect cervical cells from a subset of women. Two samples will be collected at six-month intervals from the women participating in the Aim 1 studies. Sample collection for the vaccine studies in Aim 2 will coincide with the vaccination schedule. Proposed measurements of humoral immunity include HIV-specific binding, neutralizing and ADCC antibodies. Proposed measurement of cellular immunity include CTL and CD4 lymphoproliferation and chemokine receptor expression.