Interrogating the Plasmablast Response

询问浆母细胞反应

基本信息

批准号：
8198171
负责人：
Jens Peter Wrammert
金额：
$ 42.57万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-07 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8198171
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.

该核心的目的是建立新型的单细胞技术，以分析特定的浆体对SIV疫苗的持续免疫反应或恒河猕猴中的无效。我们将生成详细的有关动力学，免疫球蛋白同种型使用和浆质的表型的信息响应在系统水平和粘膜位点都诱导，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审问正在进行的反应的免疫球蛋白库，确定针对的特定表位静脉曲张并定义了不肌抗原的非洲纤维的亲和力/亲和力/亲和力。此外，我们将表征孤立抗体的发电性预测，有关中和的广度中额以及非中和抗体介导的细胞分解机制。此外，特别是有趣的单克隆抗体，即广泛中和，也可能是未来的绝佳候选者猕猴中的被动转移经历，还具有治疗和疫苗的隐含性人类艾滋病毒的设计。