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.

本核心的目标是建立新的单细胞技术来分析特定的等离子体母细胞