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

安全有效的艾滋病毒疫苗的开发依赖于 我们识别和理解HIV-1免疫和 保护。这种关联性的确定一直受到以下因素的阻碍 经受住挑战的相对罕见的自然免疫力实例 病毒暴露的可能性。在过去的13年里，我们建立了国际 合作研究艾滋病毒-2感染的生物学及其 西非塞内加尔与艾滋病毒-1的互动。不仅HIV-2感染 不太容易通过异性和围产期途径传播，但进展 与HIV-1相比，艾滋病的传播速度要慢得多。因此，我们假设一个 相关但减弱的病毒感染可能会提供保护，使其免受更多 强毒的HIV-1病毒。1995年，我们描述了对感染艾滋病毒-2的妇女的研究。 这表明了这种保护，到目前为止，60%的保护仍在继续 这是一个观察了13年以上的队列。 HIV-2感染中假定保护作用的机制仍然存在 尚不清楚，尽管宿主细胞免疫反应可能起到重要作用。 对HIV-2感染引起的免疫反应的综合研究是 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，对CTL和T助手的评价 对HIV-2感染的反应将为理解 HIV的免疫致病机制。我们将利用我们独特的队伍 艾滋病毒-1和艾滋病毒-2的高危妇女群体，以确定 那些被重复感染的妇女和那些感染艾滋病毒-2的妇女 拥有暗示接触艾滋病毒-1的决定因素，即受保护的 个人。两组患者细胞免疫应答的比较 妇女将包括：(A)评估艾滋病毒-2的CTL反应谱 感染和确定与艾滋病毒-1的交叉反应程度；(B)罚款 绘制免疫原性HIV-2 CTL表位图；(C)评估这些CTL 功能抑制试验和(D)研究HIV-2 T辅助细胞功能和 确定这些增殖反应是否与HIV-1交叉反应。不 只有这些研究才能提供关于广度和深度的新信息 HIV-2细胞免疫反应的交叉反应，但我们也希望 将这种反应与体内HIV-1保护相关。

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.