Interrogating the Plasmablast Response

询问浆母细胞反应

• 批准号: 8681323
• 负责人: Jens Peter Wrammert
• 金额: $ 32.11万
• 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/8681323
• 关键词: Address; Adjuvant; Affinity; Animals; Antibodies; Antibody Formation; 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 Infections; HIV vaccine; Homing; Human; Immune; Immune response; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Immunoglobulin Somatic Hypermutation; Immunoglobulins; Individual; Infection; Instruction; Kinetics; Laboratories; Light; Macaca; Macaca mulatta; Mediating; Methods; Modeling; Monoclonal Antibodies; Mucous Membrane; Phenotype; Plasmablast; Property; Reagent; Recombinants; Regimen; Research Design; Reverse Transcriptase Polymerase Chain Reaction; SIV; SIV Vaccines; Sampling; Sorting - Cell Movement; Specificity; Spleen; System; Technology; Therapeutic; Time; Vaccination; Vaccine Design; Vaccines; Vagina; Viral; Virus; antibody-dependent cell cytotoxicity; direct application; env Gene Products; enzyme linked immunospot assay; gag Gene Products; human monoclonal antibodies; interest; mucosal site; neutralizing antibody; neutralizing monoclonal antibodies; new technology; novel; programs; prophylactic; prototype; rectal; research study; response; screening; 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.

该核心的目标是建立新的单细胞技术来分析特定的浆母细胞， 恒河猴对SIV疫苗接种或感染的持续免疫应答。我们将提供详细的 浆母细胞的动力学、免疫球蛋白同种型使用和表型信息 在全身水平以及粘膜部位诱导的反应，并确定这些反应如何 通过使用不同的佐剂来调节。单细胞分析将使我们能够询问 免疫球蛋白库正在进行的反应，确定特定的表位靶向的免疫球蛋白库。 浆母细胞，并定义了个体抗体对其抗原的亲和力/亲合力。此外我们 将描述分离抗体的功能特性，包括中和作用， 中和以及非中和抗体介导的细胞溶解机制。此外，特别是 有趣的单克隆抗体，即广泛中和的，也可能是未来的优秀候选者。 在恒河猴中的被动转移实验，也对治疗和疫苗有意义 设计用于人类的艾滋病毒。