ANALYZING THE HIV-SPECIFIC NEUTRALIZING ANTIBODY RESPONSE AND REPERTOIRE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在非人类灵长类动物模型中利用中和抗体(NABS)进行的被动研究表明，高剂量的NABS可以通过静脉或粘膜攻击完全阻断感染。虽然可能很难通过母体转移或接种疫苗在人类体内获得如此高水平的NAB，但有证据表明，即使是非绝育水平的NAB也可以降低体内病毒的传染性，改善疾病。非人灵长类动物模型已被用于测试被动nabs作为暴露后立即治疗的方法。本课题组的研究表明，大剂量免疫球蛋白既能控制病原性SIV，又能促进NABS的发展。我们还分析了感染另一种病毒SHV-SF162的成年和新生猕猴的NAB发展情况。我们发现，被动的nabs引发了nabs的发展，与未经治疗的对照组相比，nabs出现得更早，滴度也更高。在这项建议中，我们计划分离和鉴定从猕猴B细胞克隆的单抗，并将它们与在这些猕猴中发育的多克隆NAb进行比较。这项工作将开发有用的中和人类单抗，并将有助于理解以抗体为基础的治疗如何限制艾滋病毒的母婴传播。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.