HUMORAL AND CELLULAR IMMUNE RESPONSE TO HIV FOR VACCINE DEVELOPMENT

该项目旨在描述对人类的免疫反应。 免疫缺陷病毒(HIV)，并鉴定病毒亚片段 诱导对HIV-1、HIV-2和猿猴的保护性体液和细胞免疫 免疫缺陷病毒(SIV)。中和抗体正在研究中 在单核/巨噬细胞和T细胞系统中。病毒的保护性免疫 非传播艾滋病毒血清阳性的母亲也在接受调查。至 研究病毒异质性对中和的影响，血清型 使用匹配的血清在扎伊尔分离株中进行定义。虽然从免疫学上讲 相关的V3环(主要的HIV-1中和决定因素)有 通过交叉中和推导出的保守序列和血清型 基于V3环同调。因此，替代表位或构象表位 必须在广泛的中和中和方面发挥作用。通过以下方式增强中和 MN-V3环/HXB2D嵌合体的扎伊尔血清被归因于更好的 呈现和识别V3循环或备用 表位(S)，取决于所研究的血清。因此，它所处的上下文 提出了V3回路影响中和。中和作用的研究 体外选择的免疫耐药变异体允许进一步阐明 中和表位。到目前为止获得的逃逸突变体的变化 在V3循环之外，进一步暗示交替或构象 表位。针对HIV和SIV的细胞免疫应答低于 对几个动物系统的研究，包括恒河猴，小鼠， 还有狗。在感染HIV-2的猕猴身上看到的低病毒载量并不是 到显著的中和或细胞介导的免疫反应。 然而，从这些细胞获得的细胞毒性T淋巴细胞(CTL)克隆 受感染的猕猴将可以绘制CTL表位图。体液与细胞 免疫猕猴的介导性免疫反应正在研究中 使用带有HIV或SIV基因的牛痘、禽痘或卡介苗载体。为 未来的疫苗计划、西非的隔离和特征 逆转录病毒已经启动。这些研究将阐明病毒 这一区域的异质性，并可能发现新的逆转录病毒。

This project aims to delineate immunologic responses to the human immunodeficiency viruses (HIVs), and to identify viral subfragments which elicit protective humoral and cellular immunity to HIV-1, -2, and simian immunodeficiency virus (SIV). Neutralizing antibodies are being studied in monocyte/macrophage and T-cell systems. Protective immunity of nontransmitting HIV-seropositive mothers is also under investigation. To study the impact of viral heterogeneity on neutralization, serotypes were defined among Zairian isolates using matched sera. While immunologically related V3 loops (the principal HIV-1 neutralizing determinant) have conserved sequences, serotypes deduced by cross-neutralization were not based on V3 loop homology. Thus, alternate or conformational epitopes must play a role in broad neutralization. Enhanced neutralization by Zairian sera of an MN-V3 loop/HXB2D chimera was attributed to better presentation and recognition of either the V3 loop or an alternate epitope(s), depending on the serum studied. Thus, the context in which the V3 loop is presented affects neutralization. Study of neutralization resistant variants immune selected in vitro allows further elucidation of neutralizing epitopes. "Escape mutants' obtained to date exhibit changes outside the V3 loop, further implicating alternate or conformational epitopes. Cell mediated immune responses to the HIVs and SIVs are under investigation in several animal systems including rhesus macaques, mice, and dogs. The low viral load seen in HIV-2 infected macaques is not due to significant neutralizing or cell mediated immune responses. Nevertheless, cytotoxic T lymphocyte (CTL) clones obtained from these infected macaques will allow mapping of CTL epitopes. Humoral and cell mediated immune responses are under investigation in macaques immunized with vaccinia, avipox, or BCG vectors carrying HIV or SIV genes. For future vaccine programs, isolation and characterization of West African retroviruses have been initiated. These studies will elucidate viral heterogeneity in this region and possibly uncover novel retroviruses.