Interrogating the Plasmablast Response

询问浆母细胞反应

基本信息

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
项目类别：
财政年份：
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

项目摘要

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颖的单细胞技术来分析特定浆母细胞恒河猴对 SIV 疫苗或感染的持续免疫反应。我们将生成详细的有关浆母细胞的动力学、免疫球蛋白同种型使用和表型的信息在系统水平以及粘膜部位诱导反应，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持续反应的免疫球蛋白库，识别所针对的特定表位浆母细胞并定义单个抗体针对其抗原的亲和力/亲合力。此外我们将表征分离抗体在中和、作用广度方面的功能特性中和以及非中和、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，也可能是未来的优秀候选者恒河猴的被动转移实验也对治疗和疫苗有影响针对人类艾滋病毒的设计。