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 在目前的建议中，我们将使用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， （mRNA）或佐剂（Novavax疫苗中使用的Matrix M）。第二个问题是关于联合国的作用。 微生物对疫苗免疫的影响关于第一个问题，尽管新冠疫情发展迅速， 19种疫苗，对它们诱导先天性和 适应性反应此外，mRNA疫苗诱导的免疫应答的性质在特定的 例如患有严重过敏性疾病的人群是未知的。有趣的是，有报道称 在有特应性背景的个体中，罕见但严重的疫苗接种过敏反应。所以我们会 评估对BNT 162 b2特应性疫苗相对于健康受试者的免疫力。在矩阵M的情况下， Novavax开发的含佐剂重组COVID-19疫苗，对 由基于皂苷的Matrix-M佐剂刺激的免疫机制。我们会分析收集到的样本 来自诺华制药在南非赞助的临床试验。 该提案的第二个主题集中在微生物组对免疫力的影响， 在健康成人中接种疫苗。我们最近的工作涉及抗生素驱动的微生物群消融， 强调了微生物组在调节免疫应答中的重要作用， 季节性流感疫苗然而，成人对季节性流感疫苗的免疫反应 代表回忆反应，因为之前暴露于流感。微生物组对一个 初级免疫应答，例如对狂犬病疫苗接种的应答，尚不清楚。 这两个问题将在以下高度合作的项目和核心中得到解决：项目1（PI Pulendran）将利用多组学方法来定义驱动适应性免疫的先天反应 接种疫苗。本项目中鉴定的特征将与抗原特异性T和B细胞相关 分别在项目2（PI Davis）和项目3（PI Boyd）中评估的反应。项目2将进行深入的 对疫苗接种的抗原特异性T细胞应答的动力学分析。项目3（PI Boyd; Co-I Nadeau）将对抗原特异性B细胞应答的动力学进行深入分析， 预防针这三个项目将得到4个核心的协助。行政核心将支持 重债穷国-斯坦福中心的协调工作。临床核心（PI Nadeau）将确保 所有研究中人类受试者招募和临床表征的标准化方法; 数据管理和分析核心（PI Khatri）将提供生物信息学专业知识， 免疫监测核心（PI霍尔顿）将通过提供免疫监测测定来支持这些项目。