Interrogating the Plasmablast Response

本核心的目标是建立新的单细胞技术来分析恒河猴对SIV疫苗接种或感染的持续免疫反应中的特异性质母细胞。我们将生成关于在系统水平和粘膜部位诱导的浆母细胞反应的动力学、免疫球蛋白同型使用和表型的详细信息，并确定使用不同佐剂如何调节这些反应。单细胞分析将使我们能够询问正在进行的应答的免疫球蛋白库，确定质母细胞靶向的特定表位，并确定单个抗体对其抗原的亲和力/亲和力。此外，我们将描述分离抗体在中和、中和广度以及非中和、抗体介导的细胞溶解机制方面的功能特性。此外，特别有趣的单克隆抗体，即广泛中和抗体，也可能是未来恒河猴被动转移实验的优秀候选者，也对人类艾滋病毒的治疗和疫苗设计有影响。

The goal of this Core is to establish novel single cell technology to analyze specific plasmablasts during an ongoing immune response to SIV vaccination or infection in rhesus macaques. We will generate detailed information about the dynamics, immunoglobulin isotype useage and phenotype of the plasmablast responses induced both at a systemic level as well as at mucosal sites, and determine how these responses are modulated by the use of different adjuvants. The single cell analysis will allow us to interrogate the immunoglobulin repertoire of the ongoing response, identify the specific epitopes targeted by the plasmablasts and define the affinity/avidity ofthe individual antibodies against their antigen. Furthermore we will characterize the functional properties ofthe isolated antibodies with regards to neutralization, breadth of neutralization as well as non-neutralizing, antibody mediated cytolytic mechanisms. Furthermore, particularly interesting monoclonal antibodies, i.e. broadly neutralizing, might also be excellent candidates for future passive transfer experiments in rhesus macaques and also have implications for therapy and vaccine design for HIV in humans.