Interrogating the Plasmablast Response

询问浆母细胞反应

• 批准号: 8377227
• 负责人: Jens Peter Wrammert
• 金额: $ 32.41万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8377227
• 关键词: Address; Adjuvant; Affinity; Animals; Antibodies; Antigens; Avidity; B-Lymphocytes; Biological Assay; Blood; Blood specimen; Bone Marrow; Cell Separation; Cells; Cellular biology; Characteristics; Collaborations; Development; Epitopes; Future; Generations; Genes; Goals; HIV; HIV vaccine; Homing; Human; Immune; Immune response; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Immunoglobulins; Individual; Infection; Instruction; Laboratories; Light; Macaca; Macaca mulatta; Mediating; Methods; Modeling; Monoclonal Antibodies; Mucous Membrane; Phenotype; Plasmablast; Reagent; Recombinants; Regimen; Research Design; Reverse Transcriptase Polymerase Chain Reaction; SIV; SIV Vaccines; Sampling; Screening procedure; Sorting - Cell Movement; Specificity; Spleen; System; Technology; Therapeutic; Vaccination; Vaccine Design; Vaccines; Vagina; Viral; Virus; antibody-dependent cell cytotoxicity; env Gene Products; enzyme linked immunospot assay; gag Gene Products; human monoclonal antibodies; interest; mucosal site; neutralizing monoclonal antibodies; new technology; novel; programs; prophylactic; prototype; rectal; response; single cell analysis; therapy design; virology

The goal of this Core is to establish novel single cell technology to analyze specific plasmablasts during an ongoing immune response to SIV vaccinafion or infecfion in rhesus macaques. We will generate detailed informafion 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 targetted by the plasmablasts and define the affinity/avidity ofthe indivdual anfibodies against their antigen. Furthermore we will characterize the funcfional propoerties ofthe isolated antibodies with regards to neutralizafion, breadth of neutralizafion as well as non-neutralizing, antibody mediated cytolyfic mechanisms. Furthermore, particularly interesting monoclonal antibodies, i.e. broadly neutralizing, might also be excellent candidates for future passive transfer experiements in rhesus macaques and also have implicafions for therapy and vaccine design for HIV in humans.

这个核心的目标是建立新的单细胞技术来分析特定的成浆细胞 恒河猴对SIV疫苗或感染的持续免疫反应。我们将生成详细的 关于浆母细胞的动力学、免疫球蛋白同型利用和表型的信息 在系统水平和粘膜部位诱导的反应，并确定这些反应是如何 通过使用不同的佐剂进行调节。单细胞分析将允许我们审问 正在进行的反应的免疫球蛋白谱系，确定由 并定义单个抗体和抗体对其抗原的亲和力。此外，我们 将表征分离的抗体的功能特性，关于中和，广度 中和性以及非中和性抗体介导的细胞溶解机制。此外，特别是 有趣的单抗，即广谱中和，也可能是未来的极佳候选者 猕猴的被动移植实验，对治疗和疫苗也有意义 针对人类艾滋病病毒的设计。