RHESUS MABS FROM SHIV INFECTED MACAQUES

描述（改编自申请人的摘要）：本提案的目标将 是为了探测感染HIV-1的恒河猴的特异性B细胞库， 与嵌合猴-人类免疫缺陷病毒（SHIV），通过开发一种 大组识别包膜的恒河猴单克隆抗体（RhMAb） HIV-1的糖蛋白RhMAb将在以下方面进行表征 表位作图、菌株反应性和体外功能活性。的 恒河猴单克隆抗体将与我们现有的抗HIV-1的人单克隆抗体进行比较 以确定B细胞应答的程度 在SHIV感染的猴子中引起的与在SHIV感染的猴子中发生的相同或不同。 感染HIV-1的患者。这是一个关系到 SHIV模型与HIV-1致病机制和疫苗研究的相关性 对人类疾病的疗效。此外，具有特别 有效的体外抗HIV-1中和活性可用于谨慎的 模型化系统，以确定这些抗体是否能够保护 来自致病性SHIV攻击的幼稚猴。最后，新型MAb 可能开发出与HIV-1产生的HMAb完全不同的抗体 感染的患者，这些单克隆抗体在进一步研究 HIV-1包膜糖蛋白的结构和功能。

DESCRIPTION (Adapted from applicant's abstract):The goal of this proposal will be to probe the HIV-1 specific B cell repertoire of rhesus monkeys infected with chimeric simian-human immunodeficiency viruses (SHIVs) by developing a large panel of rhesus monoclonal antibodies (RhMAbs) that recognize envelope glycoproteins of HIV-1. The RhMAbs will be characterized with respect to epitope mapping, strain reactivity, and functional activity in vitro. The rhesus Mabs will be compared with our existing panel of human MAbs to HIV-1 surface glycoproteins in order to determine to what extent B cell responses elicited in SHIV infected monkeys are the same or different from that occurring in patients infected with HIV-1. This is an important question which bears on the relevancy of the SHIV model to studies of HIV-1 pathogenesis and vaccine efficacy to human disease. In addition, rhesus MAbs that have particularly potent neutralizing activity against HIV-1 in vitro can be used in a carefully modeled system to determine whether such antibodies are capable to protecting naïve monkeys from challenge with pathogenic SHIVs. Finally, novel MAbs may be developed which are quite different from HMAbs generated from HIV-1 infected patients and these MAbs have usefulness in further investigations of the structure and function of HIV-1 envelope glycoproteins.