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

• 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
• 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

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