HIV-2 CELLULAR IMMUNITY CROSS-REACTIVE WITH HIV-1

开发安全有效的艾滋病毒疫苗依赖于 我们识别和理解HIV-1免疫相关性的能力， 保护这种关联的识别受到以下因素的阻碍： 相对罕见的自然免疫力经受住了挑战 病毒暴露。在过去的13年里，我们建立了一个国际性的 合作研究工作，研究HIV-2感染的生物学及其 与西非塞内加尔的HIV-1相互作用。不仅是HIV-2感染 不太容易通过异性恋和围产期途径传播，但进展 与HIV-1相比，艾滋病的传播速度要慢得多。因此，我们假设， 相关但减毒的病毒感染可能提供保护， 致命的HIV-1病毒。1995年，我们描述了对HIV-2感染妇女的研究， 迄今为止，超过60%的保护仍在继续， 这个队列有13年以上的观察。 HIV-2感染中假定的保护作用的机制仍然存在 目前尚不清楚，尽管宿主细胞免疫反应可能发挥重要作用。 对HIV-2感染引起的免疫反应的全面研究是 仍然缺乏并可以支持细胞免疫反应的保护作用， 对抗HIV-1感染。此外，CTL和辅助性T细胞的评价 HIV-2感染的反应将提供重要信息， HIV的免疫发病机制我们将利用我们独特的群体优势 艾滋病毒1型和艾滋病毒2型高危妇女人口， 那些被双重感染的妇女和那些感染HIV-2的妇女， 具有提示HIV-1暴露的决定因素，即，受保护 个体比较这两组患者的细胞免疫应答， 妇女将包括：（a）评估HIV-2的CTL反应谱 感染并确定与HIV-1的交叉反应性水平;（B）精细 免疫原性HIV-2 CTL表位的定位;（c）在免疫原性HIV-2 CTL表位中评估这些CTL; 功能抑制测定和（d）研究HIV-2辅助T细胞功能和 确定这些增殖反应是否与HIV-1交叉反应。不 这些研究只会提供新的信息的广度和 HIV-2细胞免疫反应的交叉反应性，但我们也希望 将这种反应与体内HIV-1保护相关联。

The development of a safe and effective HIV vaccine is reliant on our ability to identify and understand correlates of HIV-1 immunity and protection. The identification of such correlates has been hampered by relatively rare instances of natural immunity that have withstood the challenge of viral exposure. Over the past 13 years, we have established an international collaborative research effort to study the biology of HIV-2 infection and its interaction with HIV-1 in Senegal, West Africa. Not only is HIV-2 infection less readily transmitted by heterosexual and perinatal routes, but progression to AIDS is substantially slower compared to HIV-1. Thus, we hypothesized that a related yet attenuated virus infection might provide protection from the more virulent HIV-1 virus. In 1995, we described studies of HIV-2 infected women that demonstrated such protection and, to date, >60% protection continues in this cohort with 13+ years of observation. The mechanisms for the postulated protective effect in HIV-2 infection remains unclear, although host cellular immune responses may play an important role. Comprehensive studies of the immune responses elicited in HIV-2 infection are still lacking and could support the protective role of cellular immune response against HIV-1 infection. In addition, the evaluation of CTL and T helper responses in HIV-2 infection will offer crucial information in understanding the immunopathogenesis of HIV. We will take advantage of our unique cohort population of women at high risk for both HIV-1 and HIV-2 in order to identify those women that have been superinfected and those HIV-2 infected women that possess determinants suggestive of HIV-1 exposure, i.e., the protected individuals. Comparison of the cellular immune responses in these two groups of women will include: (a) evaluating the spectrum of CTL responses in HIV-2 infection and determining the level of cross-reactivity with HIV-1; (b) fine mapping of the immunogenic HIV-2 CTL epitopes; (c) assessing these CTLs in a functional inhibition assay and (d) studying the HIV-2 T helper function and determining if these proliferative responses are cross-reactive with HIV-1. Not only will these studies provide new information on the breadth and cross-reactivity of the HIV-2 cellular immune responses, but we also hope to correlate such responses with HIV-1 protection in vivo.