Interrogating the Plasmablast Response

询问浆母细胞反应

基本信息

批准号：
8883357
负责人：
Jens Peter Wrammert
金额：
$ 32.5万
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 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8883357
关键词：
Address Adjuvant Affinity Animals Antibodies Antibody Response 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 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 vaccine trial 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 vaccination or infection in rhesus macaques. We will generate detailed information 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 targeted by the plasmablasts and define the affinity/avidity ofthe individual antibodies against their antigen. Furthermore we will characterize the functional properties ofthe isolated antibodies with regards to neutralization, breadth of neutralization as well as non-neutralizing, antibody mediated cytolytic mechanisms. Furthermore, particularly interesting monoclonal antibodies, i.e. broadly neutralizing, might also be excellent candidates for future passive transfer experiments in rhesus macaques and also have implications 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，以分析对SIV疫苗接种或恒河猕猴感染的持续免疫反应期间的特定浆膜。我们将生成有关动态，免疫球蛋白同种型的使用以及在系统水平和粘膜位点诱导的浆膜反应的表型的详细信息，并确定如何通过使用不同辅助剂调节这些响应。单细胞分析将使我们能够询问正在进行的反应的免疫球蛋白库，确定浆膜靶向的特定表位，并定义各个抗体抗原的亲和力/伴随。此外，我们将在中和，中和以及非中和抗体介导的细胞溶解机制方面表征分离的抗体的功能特性。此外，特别有趣的单克隆抗体（即广泛中和）也可能是恒河猕猴未来被动转移实验的出色候选者，并且对人类的HIV的治疗和疫苗设计也有影响。