Systems biological assessment of B cell responses to vaccination

B 细胞对疫苗接种反应的系统生物学评估

基本信息

批准号：
10584576
负责人：
Scott Dexter Boyd
金额：
$ 54.18万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-07 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584576
关键词：
2019-nCoV Ablation Acute Adjuvant Adverse reactions Affect Affinity Allergic Antibiotic Therapy Antibiotics Antibodies Antibody Response Antibody titer measurement Antigens Avidity B-Cell Antigen Receptor B-Lymphocytes B-cell receptor repertoire sequencing Basophils Binding Biological Assay Blood Bone Marrow COVID-19 COVID-19 pandemic COVID-19 vaccine Cells Clinical Clone Cells Collaborations DNA Data Analyses Development Ensure Epitopes Fine needle aspiration biopsy Food Hypersensitivity Future Glycoproteins Human Humoral Immunities Immune response Immunity Immunoglobulin G Immunoglobulin M Immunology Individual Infection Investigation Label Longevity Measures Memory B-Lymphocyte Methods Monitor Monoclonal Antibodies Natural Immunity Participant Pathogenicity Pathway interactions Phenotype Plasma Cells Plasmablast Polyethylene Glycols Population RNA vaccination RNA vaccine Rabies Rabies Vaccines Reaction Recombinant Proteins Recording of previous events Reporting Role SARS-CoV-2 antigen Sampling Serology Shapes Specificity Specimen Structure of germinal center of lymph node T-Lymphocyte Vaccination Vaccinee Vaccines Variant Viral Virus Virus Diseases adaptive immunity biological systems clinically significant combat coronavirus disease data management in vitro Assay lipid nanoparticle lymph nodes microbiome microbiota monoclonal antibody production multiplex assay novel novel coronavirus pathogen peripheral blood recruit response transcriptome vaccination strategy vaccine development vaccine platform vaccine response vaccinology variants of concern

2019-nCoV Ablation Acute Adjuvant Adverse reactions Affect Affinity Allergic Antibiotic Therapy Antibiotics Antibodies Antibody Response Antibody titer measurement Antigens Avidity B-Cell Antigen Receptor B-Lymphocytes B-cell receptor repertoire sequencing Basophils Binding Biological Assay Blood Bone Marrow COVID-19 COVID-19 pandemic COVID-19 vaccine Cells Clinical Clone Cells Collaborations DNA Data Analyses Development Ensure Epitopes Fine needle aspiration biopsy Food Hypersensitivity Future Glycoproteins Human Humoral Immunities Immune response Immunity Immunoglobulin G Immunoglobulin M Immunology Individual Infection Investigation Label Longevity Measures Memory B-Lymphocyte Methods Monitor Monoclonal Antibodies Natural Immunity Participant Pathogenicity Pathway interactions Phenotype Plasma Cells Plasmablast Polyethylene Glycols Population RNA vaccination RNA vaccine Rabies Rabies Vaccines Reaction Recombinant Proteins Recording of previous events Reporting Role SARS-CoV-2 antigen Sampling Serology Shapes Specificity Specimen Structure of germinal center of lymph node T-Lymphocyte Vaccination Vaccinee Vaccines Variant Viral Virus Virus Diseases adaptive immunity biological systems clinically significant combat coronavirus disease data management in vitro Assay lipid nanoparticle lymph nodes microbiome microbiota monoclonal antibody production multiplex assay novel novel coronavirus pathogen peripheral blood recruit response transcriptome vaccination strategy vaccine development vaccine platform vaccine response vaccinology variants of concern

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项目摘要

ABSTRACT – Project 3 The focus of Project 3 is to study antigen-specific B cell and plasma cell responses in the context of two timely and fundamental topics in vaccinology: (i) Immunology of COVID-19 vaccines, and (ii) the impact of the microbiota on immune responses to vaccination. The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 (CoV-2), and the vaccines developed to combat this pathogen, have underscored a need for greater understanding of primary antibody responses in humans. We will use a systematic panel of cutting- edge humoral immunity analyses to thoroughly characterize antibodies elicited by two CoV-2 vaccines, and the B cell and plasma cell clonal populations required for B cell memory and sustained antibody titers. Our focus will be on the serological, B cell and plasma cell responses elicited by a lipid nanoparticle mRNA vaccine (Pfizer-BioNTech), and a Matrix M-adjuvanted recombinant protein vaccine (Novavax). Combining these analyses with studies of innate immunity (Project 1) and T cell (Project 2) responses to these vaccines should highlight cellular mechanisms correlated with the strength and durability of antibody responses. Rare serious anaphylactoid adverse reactions have been reported for mRNA vaccines, particularly in individuals with a history of food allergy, and those with IgG antibodies specific for polyethylene glycol (PEG). We will examine potential B cell contributions to these anaphylactoid reactions, using specimens from affected individuals who received SARS-COV-2 mRNA vaccines. Finally, we will address the role of the microbiome on humoral immunity to vaccination, with a similar strategy of serological, memory B cell and plasma cell analyses in participants with or without temporarily ablated microbiota following antibiotic treatment. Of particular importance in the aforementioned studies, we will not only analyze peripheral blood B cells and plasmablasts, but also monitor lymph node germinal center reactions by fine-needle aspiration, and sample bone marrow plasma cells in the same participants, to comprehensively study humoral immunity to vaccination in humans. The combined impact of these investigations will likely be clinically significant in guiding the development of future vaccination strategies by uncovering the B cell and plasma cell specificities, differentiation pathways, and longevity stimulated by new SARS-CoV-2 vaccine platforms, and in clarifying the role of the microbiome in vaccine responses to novel antigens.

摘要 - 项目3 项目3的重点是在两个及时研究抗原特异性B细胞和浆细胞反应疫苗学的基本主题：（i）Covid-19疫苗的免疫学，以及（ii）微生物群对疫苗接种的免疫反应。新型冠状病毒引起的19009年大流行 SARS-COV-2（COV-2）和为了对抗这种病原体而开发的疫苗已经强调了对人类的主要抗体反应的更多了解。我们将使用系统的剪裁面板 - 边缘体液免疫学分析以彻底表征两种COV-2疫苗引起的抗体， B细胞记忆和持续抗体所需的B细胞和浆细胞克隆群滴度。我们的重点将放在脂质纳米粒子mRNA引起的血清学，B细胞和浆细胞反应上疫苗（辉瑞-biontech）和基质M-辅助重组蛋白疫苗（Novavax）。结合这些对先天免疫（项目1）和T细胞（项目2）对这些疫苗的反应的分析应突出显示与抗体反应的强度和耐用性相关的细胞机制。罕见的认真已经报道了对mRNA疫苗的过敏反应反应，特别是在患有病史的个体中食物过敏，以及对聚乙烯甘氨酸（PEG）特异的IgG抗体的食物过敏。我们将检查潜力 B细胞对这些过敏反应的贡献，使用受影响个体的标本接受了SARS-COV-2 mRNA疫苗。最后，我们将解决微生物组在体液中的作用对疫苗接种的免疫力，具有类似的血清学，记忆B细胞和浆细胞分析的策略在抗生素治疗后有或没有临时消融微生物群的参与者中。特别在预测研究中的重要性，我们不仅会分析外周血B细胞和浆质。而且还通过细针抽吸和样品骨监测淋巴结生发中心反应同一参与者中的骨髓浆细胞，以全面研究人类疫苗接种。这些调查的综合影响可能在指导发展方面具有临床意义通过发现B细胞和浆细胞的规格，分化途径以及新的SARS-COV-2疫苗平台刺激了寿命疫苗对新抗原的反应。