Core C: B Cell Core

核心C：B细胞核心

基本信息

批准号：
10731279
负责人：
Kristina De Paris
金额：
$ 26.78万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731279
关键词：
Adult Antibodies Antibody Avidity Antibody Repertoire Antibody Response Antigens Autologous Avidity B-Cell Antigen Receptor B-Cell Development B-Lymphocytes B-cell receptor repertoire sequencing Bar Codes Binding Biological Assay Biometry Bone Marrow Cell Lineage Cells Collaborations Computer Analysis Data Development Dose Engineering Environment Enzyme-Linked Immunosorbent Assay Epitopes Evolution Flow Cytometry Future Generations Goals HIV HIV vaccine HIV-1 Immune Immune response Immune system Immunity Immunization Infant Infection Laboratories Lead Life Lymphoid Tissue Macaca Macaca mulatta Mediating Medicine Messenger RNA Molecular Profiling Monoclonal Antibodies Natural Immunity Nature Phenotype Plasma Plasma Cells Predisposition Process Proteomics Regimen Reproducibility Resources Running Serum Sorting Specificity Surface Plasmon Resonance Technology Time Vaccinated Vaccination Vaccine Design Vaccinee Vaccines Virus Work autoreactivity experience genetic signature genomic platform innovation lymph nodes microbial microbiome microorganism interaction neutralizing antibody next generation sequencing nonhuman primate programs response single-cell RNA sequencing time use tool transcriptomics transmission process vaccine evaluation vaccine immunogenicity vaccine strategy

项目摘要

ABSTRACT – B Cell Core Early development of bNAbs in infants suggest potentially distinct mechanisms in the generation of antibody breadth due to the highly dynamic nature of the infant immune system. Moreover, we have observed elicitation of bNAb precursors in infant rhesus monkeys with germline-targeting HIV Env SOSIP immunization. We hypothesize that induction of bnAb precursor B cells using germline-targeting HIV Env SOSIP immunogens requires specific innate and microbial interactions which are modifiable to enhance future HIV vaccine strategies, particularly in early life. In this context, we propose a B Cell Core that will perform in-depth quantification and characterization of the plasma and B cell responses after BG505 SOSIP GT1.1 immunizations in infant macaques over time through i) the quantification of the functional activity, avidity and target epitope of polyclonal plasma antibody responses (Aim 1) and ii) single cell RNA sequencing of antigen-specific B cell analysis (Aim 2) to evaluate the evolution of vaccine-elicited HIV bNAb precursors and relate these responses to innate immunity (Project 1) and microbial interactions (Project 2). To accomplish this goal, the B Cell Core will draw on the extensive experience and unique resources in antibody and B cell response characterization of the B Cell Core Leader Dr. Marit van Gils at Amsterdam UMC and Dr. Sallie Permar at Weill Cornell Medicine.

摘要 - B细胞核心婴儿的早期开发在婴儿中提出了抗体产生的潜在不同机制由于婴儿免疫系统的高度动态性质，广度。而且，我们观察到启发婴儿恒河猴的BNAB前体具有靶向种系的HIV ENV SOSIP免疫。我们假设使用靶向种系HIV Env SOSIP免疫原的BNAB前体B细胞诱导BNAB前体B细胞需要特定的先天和微生物相互作用，这些相互作用可修改以增强未来的HIV疫苗策略，在这种情况下，我们提出了一个B细胞核，该核心将执行深入的定量和 BG505 SOSIP GT1.1免疫接种后血浆和B细胞反应的表征随着时间的流逝，猕猴通过i）多克隆的功能活性，亲戚和靶表稳定性的数量血浆抗体反应（AIM 1）和II）抗原特异性B细胞分析的单细胞RNA测序（AIM 2）评估疫苗吸引的HIV BNAB前体的演变，并与先天的反应免疫（项目1）和微生物相互作用（项目2）。为了实现这一目标，B细胞核将绘制关于B细胞的抗体和B细胞反应表征的丰富经验和独特资源阿姆斯特丹UMC的Marit Van Gils博士和Weill Cornell Medicine的Sallie Permar博士。