RHESUS MABS FROM SHIV INFECTED MACAQUES

描述(改编自申请人的摘要)：本提案的目标将 将探索感染HIV-1的猕猴的HIV-1特异性B细胞库 通过开发一种嵌合的猿猴-人类免疫缺陷病毒(SHIV) 识别包膜的大群恒河猴单抗(RhMAbs) HIV-1的糖蛋白。RhMAb将根据以下方面进行表征 表位定位、菌株反应性和体外功能活性。这个 猕猴单抗将与我们现有的针对HIV-1的人类单抗小组进行比较 表面糖蛋白以确定B细胞在多大程度上反应 在感染SIV的猴子身上引发的病毒与发生的相同或不同 在感染HIV-1的患者中。这是一个事关重大的问题 SIV模型与HIV-1致病机制和疫苗研究的相关性 对人类疾病的功效。此外，恒河猴单抗具有特别的 有效的体外中和抗HIV-1活性可用于谨慎使用 建模系统，以确定此类抗体是否能够保护 保护猴子免受病原性肺炎的攻击。最后，新奇单抗 可能开发出与HIV-1产生的HMAb非常不同的HMAb 感染患者和这些单抗在进一步的研究中是有用的 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.