ANALYZING THE HIV-SPECIFIC NEUTRALIZING ANTIBODY RESPONSE AND REPERTOIRE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在HIV的非人灵长类动物模型中利用中和抗体（NAb）的被动研究表明，高剂量的NAb可以通过静脉内或粘膜攻击完全阻断感染。 虽然通过母体转移或疫苗接种可能难以在人体中获得如此高水平的NAb，但有证据表明，即使是非灭菌水平的NAb也可以降低体内病毒的感染性并改善疾病。 非人灵长类动物模型已被用于测试被动NAb作为暴露后立即治疗。 本研究表明，高剂量IgG既能控制致病性SIV，又能促进NAb的形成。我们还分析了感染另一种病毒SHIV-SF 162的成年和新生猕猴中NAb的发展。我们发现，被动NAb引发的NAb的发展，出现更快，更高的滴度比那些在未经处理的对照组。在这个提议中，我们计划分离和表征从猕猴B细胞克隆的单个单克隆抗体（mAb），并将其与在这些猕猴中开发的多克隆NABS进行比较。 这项工作将开发有用的中和人类单克隆抗体，并将有助于了解基于抗体的治疗如何限制艾滋病毒的母婴传播。 本项目使用猪尾猕猴存档的组织和血液样本。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Passive studies utilizing neutralizing antibodies (NAbs) in non-human primate models for HIV have shown that high doses of NAbs can fully block infection by either intravenous or mucosal challenge. Although it may be difficult to attain such high levels of NAbs in humans through maternal transfer or vaccination, there is evidence that even non-sterilizing levels of NAbs can reduce the infectivity of viruses in vivo and ameliorate disease. Non-human primate models have been used to test passive NAbs as immediate post-exposure treatments. Our group showed that high dose IgG can both control the pathogenic SIV and also accelerate the development of NAbs. We have also analyzed the development of NAbs in adult and newborn macaques infected with another virus, SHIV-SF162. We found that passive NAbs triggered the development of NAbs that appeared sooner and were higher in titer than those that developed in untreated controls. In this proposal, we plan to isolate and characterize individual monoclonal antibodies (mAbs) cloned from macaque B cells and to compare them with the polyclonal NAbs that develop in these macaques. This work will develop useful neutralizing human mAbs and will contribute to understanding how antibody-based therapy can limit Mother-to-child transmission of HIV. This project uses tissues and blood samples archived from Pigtail Macaques.