Resource for Nonhuman Primate Cell Depleting Antibodies

描述（由申请人提供）：非人灵长类动物（NHPs）为探索传染性和非传染性疾病的发病机制以及测试无法在啮齿动物中进行评估的新疗法和疫苗提供了强大的动物模型。在过去的十年里，NIH对非人灵长类动物的资助增加了一倍。然而，在许多情况下，这些模型的效用受到体外诊断和体内特定免疫功能调节试剂的可用性的限制。在之前的资助期间，我们建立了NIH非人灵长类动物试剂资源，这是一个鉴定和/或开发单克隆抗体的项目，包括新的小鼠-人嵌合重组单克隆抗体，全人单克隆抗体和恒河猴受体/人Ig融合蛋白，这些蛋白在体内消耗特定淋巴细胞亚群或靶向特定免疫功能。我们还建立了大规模生产试剂的工艺，并优化了它们的使用。在最初的奖励期间，我们分发了90,000毫克纯化单克隆抗体，支持超过60个NIH拨款或代表8个NIH研究所或中心的校内项目。

DESCRIPTION (provided by applicant): Nonhuman primates (NHPs) provide powerful animal models for exploring the pathogenesis of infectious and noninfectious diseases, and for testing of new therapies and vaccines that cannot be evaluated in rodents. Over the past decade, the number of NIH grants employing nonhuman primates has doubled. However, the utility of these models in many cases is limited by the availability of reagents for in vitro diagnostics and for in vivo modulation of specific immune functions. During the previous funding period of this grant, we established the NIH Nonhuman Primate Reagent Resource, a program for identifying and/or developing monoclonal antibodies, including new mouse-human chimeric recombinant monoclonal antibodies, fully-human monoclonal antibodies and rhesus receptor/human Ig fusion proteins that deplete specific lymphocyte subpopulations or target specific immune functions in vivo. We also established processes for large-scale production of reagents and optimized their use. During this initial award period, we distributed 90,000 milligrams of purified monoclonal antibody supporting more than 60 NIH grants or intramural programs representing 8 NIH institutes or centers. The need for these unique reagents has grown steadily since the initiation of this program. In addition, the potential has emerged to develop new reagents with reduced antigenicity, longer duration of effect in vivo and more focused targeting of lymphocyte subpopulations. To continue support of nonhuman primate models across multidisciplinary scientific programs we will: 1) Produce and distribute recombinant antibodies and fusion proteins developed during the previous funding period, 2) Identify and/or develop reagents, including recombinant (chimeric, humanized and primatized) mAbs, with new specificities and functions as directed by a scientific advisory committee, 3) Develop macaque IgG vectors for generating recombinant rhesus antibodies and rhesus Ig-Fc fusion proteins, and assess the in vivo biological properties of recombinant rhesus lgG1, lgG2 and lgG4 antibodies, 4) Explore methods of increasing recombinant antibody plasma half-life by increasing affinity for FcRn, and 5) Determine if experimental lymphocyte depletion reactivates viruses that are endemic in captive NHPs potentially affecting experimental outcome or having public health considerations.