Female genital tract immunity and HIV vaccine responses

越来越多的证据表明，来自不同地域、通过性接触感染艾滋病毒风险很高的妇女，由于获得了对该病毒的免疫力，可能受到保护而不受感染。一些研究现已证明，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HIV预防性疫苗的开发，并可能在未来的疫苗试验中深入了解靶向生殖道作为HIV传播免疫途径的可能效用。这项建议有两个目的。第一个目的是描述和比较现有妇女群体生殖道中艾滋病毒特异性体液和细胞反应。这项建议有两个目的。第一个目标是确定和比较现有妇女群体生殖道中艾滋病毒特异性体液和细胞反应的特征：来自WISH/CDC Vision项目研究的64名未感染妇女，她们通过性传播高度接触艾滋病毒;来自COIP/NIDA针头交换研究的33名未感染妇女，她们父母接触艾滋病毒的比例高，性接触艾滋病毒的比例低;来自UIC医学中心妇科诊所的33名妇女几乎没有或没有暴露于HIV的风险;来自芝加哥WIHS研究的33名HIV感染妇女。第二项研究的目的是测量参与艾滋病毒疫苗有效性试验的妇女生殖道中艾滋病毒特异性体液和细胞反应。将从WISH项目正在进行的VaxGen VAX 0004疗效试验中招募30名女性。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名妇女。将从参与这些粘膜免疫研究的所有女性中收集CVL、宫颈芯、血清和风险评估。将使用细胞刷从一部分女性中收集宫颈细胞。将每隔6个月从参与目标1研究的女性中采集两份样本。目标2中疫苗研究的样本采集将与疫苗接种时间表一致。建议测量体液免疫包括HIV特异性结合，中和和ADCC抗体。建议的细胞免疫测量包括CTL和CD 4淋巴细胞增殖和趋化因子受体表达。

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.