Human and monkey Mabs to Quaternary Epitopes

该项目的主要目标是开发具有广泛反应性和有效性的人和恒河猴 识别四级中和表位的单克隆抗体（HMAb和RhMAb） （QNE）。这组表位只是最近才受到关注，主要是因为适合 以前没有检测这种抗体的方法。现在可以确定 血清中含有这种新型抗体的患者。反映对以下的免疫应答的MAb QNE将被要求精确定义其结构。在这个项目中，我们将使用改进的 产生识别QNE的人类和恒河猴单克隆抗体的方法， 了解QNE结构和功能的重要试剂。人类研究将涉及 CAPRISA队列患者，如CAP 256，一种南非患者，具有针对QNE的高滴度， C亚型分离株，以及在品特实验室研究的美国患者。同样，我们将生产 来自猕猴的猴MAb，由于感染SHIV而产生QNE定向抗体 表达QNE的保守VIA/2决定簇。单克隆抗体将用于定位表位， QNE的结构分析。该项目将涉及与所有 个别项目和核心。

The major goal of this project is to develop broadly reactive and potent human and rhesus monkey monoclonal antibodies (HMAbs and RhMAbs) recognizing quaternary neutralization epitopes (QNE). This group of epitopes has only very recently received attention, mainly because suitable methods for detecting such antibodies were not previously available. It is now feasible to identify patients whose sera contain this novel class of antibody. MAbs reflecting immune responses to QNEs will be required to precisely define their structure(s). In this project, we will use improved methodologies generating human and rhesus MAbs recognizing QNEs that will contribute critically important reagents for understanding QNE structure and function. Human studies will involve CAPRISA cohort patients, such as CAP256, a South African patient with high titers against QNEs of subtype C isolates, as well as U.S. patients studied in the Pinter lab. Likewise, we will produce monkey MAbs from macaques making QNE directed antibodies as a result of infection with SHIVs expressing conserved VIA/2 determinants of QNEs. MAbs will be used in mapping epitopes and structural analysis of QNEs. This project will involve intense collaborative interactions with all the individual Projects and Cores.