IMMUNIZATION AND HUMORAL RESPONSE TO HIV1 896 ENV

HIV-1包膜蛋白(Env)以寡聚复合体形式存在于 病毒粒子和受感染细胞的表面。从我们的实验室和几个 也有人指出，环境寡聚体结构具有重要的作用。 对理解体液免疫反应的影响，很可能 对于引发广泛的交叉反应、中和很重要 抗体。然而，也很明显，许多疫苗工作已经 集中在适应HIV-1毒株的T细胞系，包括我们的一些 很可能是被误导了。相反，包膜蛋白来源于 应对初级病毒分离株进行原地研究。近期 趋化因子受体领域的突破进一步有助于 突出实验室适应的病毒分离株和主要病毒分离株之间的差异。 因此，我们将重点转向主要的病毒分离株， 尤其是双嗜性病毒株89.6。我们已经开发出 获得毫克量纯化的、可溶的、单体的技术 和低聚形式的原生包膜蛋白，并建议和高度 一个合作项目，旨在测试DNA和 采取严格的亚单位疫苗接种策略。我们将产生， 鉴定并以毫克量生产原发HIV-1膜蛋白 蛋白质。然后，这些蛋白质将被我们的同事们用在一系列 免疫研究的成果。其中，也许最重要的是那些 这将试图赋予恒河猴一种致命的免疫力 挑战与希夫89.6便士。然后，我们将协助描述 疫苗接种过程中和病毒攻击后的体液免疫反应 无论是这个项目还是其他合作项目。此外，我们还将 研究病毒主要包膜蛋白的抗原性结构 生产单抗到寡聚体89.6，并将研究抗体 根据我们对中和机制的快速增长的了解 环境-趋化因子受体的相互作用。

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.