IMMUNIZATION AND HUMORAL RESPONSE TO HIV1 896 ENV

HIV-1包膜（env）蛋白作为寡聚复合物存在于 病毒粒子和受感染细胞的表面。从我们的实验室和几个 其他人已经指出，env寡聚体结构具有重要的 对理解体液免疫反应的影响， 对于引发广泛的交叉反应，中和 抗体的然而，也很明显，许多疫苗工作， 集中在T细胞系适应的HIV-1菌株，包括我们的一些 自己，很可能被误导了。相反，env蛋白来源于 应在其位置研究主要病毒分离株。最近 趋化因子受体领域的突破进一步有助于 强调了实验室适应病毒分离株和原代病毒分离株之间的差异。 因此，我们将重点转移到了原始病毒分离株上， 特别是双嗜性病毒株89.6。我们已经开发 技术，以获得毫克量的纯化的，可溶的，单体 以及初级env蛋白的寡聚体形式，并提出和高度 一个合作项目，旨在测试DNA和 亚单位疫苗接种策略以严格的方式。我们将创造， 表征并以毫克数量生产原HIV-1包膜 proteins.这些蛋白质将被我们的同事用于一系列 免疫研究。其中，最重要的可能是 这将试图赋予恒河猴免疫力， 用SIV 89.6P进行挑战。然后我们将协助描述 疫苗接种期间和病毒攻击后的体液免疫应答 在这个项目和其他合作项目中。此外，我们将 研究原代病毒env蛋白的抗原结构， 生产MABs寡聚89.6，并将研究抗体 鉴于我们对以下方面的知识迅速增加， env-趋化因子受体相互作用。

The HIV-1 envelope (env) protein exists as an oligomeric complex on the surface of virions and infected cells. Work from our lab and several others has indicated that env oligomeric structure has important implications for understanding the humoral immune response, and may well be important for eliciting broadly cross-reactive, neutralizing antibodies. However, it is also clear that much vaccine work that has concentrated on T-cell line adapted HIV-1 strains, including some of our own, has probably been misguided. Rather, env proteins derived from primary virus isolates should be studied in their place. Recent breakthroughs in the chemokine receptor field have further served to highlight differences between lab adapted and primary virus isolates. Therefore, we have shifted our focus to primary virus isolates, particularly the dual-tropic virus strain 89.6. We have developed techniques to obtain milligram quantities of purified, soluble, monomeric and oligomeric forms of primary env proteins, and propose and highly collaborative project designed to test the efficacy of both DNA and subunit vaccination strategies in a rigorous manner. We will generate, characterize, and produce in milligram quantities primary HIV-1 env proteins. These proteins will then be used by our colleagues in a series of immunization studies. Of these, perhaps the most important are those that will attempt to confer immunity in rhesus macaques to a lethal challenge with SHIV 89.6P. We will then assist in the characterization of the humoral immune response during vaccination and after virus challenge both for this and other collaborative projects. Furthermore, we will investigate the antigenic structure of primary virus env proteins by producing MABs to oligomeric 89.6, and will investigate antibody neutralizing mechanisms in light of our rapidly increasing knowledge of env-chemokine receptor interactions.