Systems biological assessment of innate and adaptive immunity to vaccination

对疫苗接种的先天性和适应性免疫的系统生物学评估

• 批准号: 10584552
• 负责人: BALI PULENDRAN
• 金额: $ 216.82万
• 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/10584552
• 关键词: Ablation; Address; Adjuvant; Adult; Algorithms; Allergic Disease; Allergic Reaction; Antibiotics; Antigens; Automobile Driving; Award; B-Lymphocytes; Bioinformatics; Biological Assay; Biological Markers; COVID-19 vaccine; Cells; Clinical; Clinical Trials; Computer Models; Cytometry; Data Analyses; Data Security; Data Storage and Retrieval; Databases; Development; Ensure; Exposure to; Human; Immune; Immune response; Immunity; Immunologic Monitoring; Immunologic Stimulation; Immunology; Individual; Influenza; Messenger RNA; Molecular Profiling; National Institute of Allergy and Infectious Disease; Natural Immunity; Nature; Pfizer-BioNTech COVID-19 vaccine; Plasma; Population; Predisposition; RNA vaccine; Rabies; Recombinants; Recommendation; Reporting; Research Personnel; Research Project Grants; Role; Sampling; Saponins; Services; South Africa; South African; Special Population; Standardization; System; T cell response; T-cell receptor repertoire; Technology; Vaccination; Vaccines; Validation; Work; adaptive immunity; antigen-specific T cells; biological systems; cytokine; data integration; data management; data submission; epigenomics; human subject; immunoregulation; influenza virus vaccine; insight; metabolomics; microbiome; microbiota; multiple omics; new technology; novel; public database; recruit; response; seasonal influenza; single cell analysis; transcriptomics; vaccine development; vaccinology

ABSTRACT – Overall Component In the current proposal we will use a systems vaccinology approach to address two fundamental issues in vaccinology. The first issue concerns the immunology of COVID-19 vaccines, which utilize novel platforms (mRNA) or adjuvants (Matrix M used in the Novavax vaccine). The second issue is related to the role of the microbiome on vaccine immunity. With respect to the first issue, despite the rapid development of COVID- 19 vaccines, there is a paucity of understanding about the mechanisms by which they induce innate and adaptive responses. Furthermore, the nature of the immune response induced by mRNA vaccines in special populations such as those with serious allergic disease is unknown. Interestingly, there have been reports of rare but severe allergic reactions to vaccination, in individuals with an atopic background. Therefore, we will assess immunity to the BNT162b2 vaccine atopic versus healthy subjects. In the case of the Matrix-M adjuvanted recombinant COVID-19 vaccine developed by Novavax, there is a paucity of understanding of immune mechanisms stimulated by the saponin-based Matrix-M adjuvant. We will analyze samples collected from a Novavax sponsored clinical trial in South Africa. The second theme of the proposal is focused on the impact of the microbiome on immunity to vaccination in healthy adults. Our recent work involving antibiotics driven ablation of the microbiota has highlighted an important role for the microbiome in modulating immune responses to vaccination with the seasonal influenza vaccine. However, the immune response against seasonal influenza vaccine in adults represents a recall response, because of prior exposure to influenza. The impact of the microbiome on a primary immune response, such as the response to rabies vaccination, is unknown. These two issues will be addressed in the following highly collaborative projects and cores: Project 1 (PI Pulendran) will utilize a multi-omics approach to define innate responses driving adaptive immunity immunity to vaccination. The signatures identified in this project will be correlated with antigen-specific T and B cell responses assessed in Projects 2 (PI Davis) and 3 (PI Boyd), respectively. Project 2 will perform an in-depth analysis of the dynamics of the antigen-specific T cell responses to vaccination. Project 3 (PI Boyd; Co-I Nadeau) will perform an in-depth analysis of the dynamics of the antigen-specific B cell responses to vaccination. The three projects will be assisted by 4 cores. The Administrative Core will support the coordination efforts across the HIPC-Stanford Center. The Clinical Core (PI Nadeau) will ensure a standardized approach in the recruitment and clinical characterization of human subjects in all studies; the Data Management and Analysis Core (PI Khatri) will provide bioinformatics expertise, and the Human Immune Monitoring Core (PI Holden) will support the projects by providing immune monitoring assays.

摘要-整体组件