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: 10419275
• 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/10419275
• 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; Immunology; Individual; Influenza; Investigation; 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; 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; Time; Vaccination; Vaccines; Validation; Work; adaptive immunity; antigen-specific T cells; base; biological systems; cytokine; data integration; data management; data submission; epigenomics; human subject; 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 在当前的提案中，我们将使用一种系统疫苗学方法来解决两个基本问题 疫苗学。第一个问题涉及Covid-19疫苗的免疫学，该疫苗利用了新型平台 （mRNA）或调节器（Novavax疫苗中使用的基质M）。第二个问题与 疫苗免疫的微生物组。关于第一个问题，请迅速发展共同发展 19疫苗，对它们影响与生俱来的机制的理解很少 自适应反应。此外，特殊mRNA疫苗引起的免疫反应的性质 诸如严重过敏性疾病的人群尚不清楚。有趣的是，有报道 在具有原位背景的个体中，对疫苗接种的罕见但严重的过敏反应。因此，我们会的 评估对BNT162B2疫苗与健康受试者的免疫力。如果是矩阵-M Novavax开发的佐剂重组共同COVID-19疫苗，对 基于皂苷的基质-M调节剂刺激的免疫机制。我们将分析收集的样品 来自南非的Novavax赞助临床试验。 该提案的第二个主题集中于微生物组对免疫的影响 健康成年人的疫苗接种。我们最近涉及抗生素的工作驱动了微生物群的消融 强调了微生物组在调节对疫苗接种免疫反应中的重要作用 季节性影响疫苗。但是，成年人对季节性影响疫苗的免疫响应 代表召回响应，因为事先暴露于影响力。微生物组对 原发性免疫反应，例如对狂犬病疫苗接种的反应，尚不清楚。 这两个问题将在以下高度协作的项目和核心中解决：项目1（PI Pulendran）将利用一种多词的方法来定义驱动适应性免疫史的先天反应 接种疫苗。该项目中确定的签名将与抗原特异性T和B细胞相关 在项目2（PI Davis）和3（PI Boyd）中评估的响应。项目2将执行深入 分析抗原特异性T细胞对疫苗接种的动力学。项目3（pi boyd; co-i Nadeau）将对抗原特异性B细胞反应的动力学进行深入分析 疫苗接种。这三个项目将由4个核心协助。行政核心将支持 HIPC-Stanford中心的协调工作。临床核心（Pi Nadeau）将确保 在所有研究中，人类受试者的招募和临床表征中的标准化方法；这 数据管理和分析核心（Pi Khatri）将提供生物信息学专业知识，人类 免疫监测核心（PI Holden）将通过提供免疫监测测定法支持项目。