Systems biological assessment of innate responses to vaccination

对疫苗接种先天反应的系统生物学评估

• 批准号: 10584566
• 负责人: BALI PULENDRAN
• 金额: $ 51.25万
• 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/10584566
• 关键词: Ablation; Address; Adjuvant; Adult; Allergic Reaction; Antibiotics; Antibody Response; Antiviral resistance; B-Lymphocytes; COVID-19 vaccination; COVID-19 vaccine; Cells; Clinical Trials; Cytometry; Dendritic Cells; Dengue; Development; Epigenetic Process; Exposure to; Fine needle aspiration biopsy; Frequencies; Human; Hypersensitivity; Immune response; Immunity; Immunologics; Immunology; Impairment; Individual; Influenza; Influenza A Virus, H5N1 Subtype; Innate Immune Response; Memory; Messenger RNA; Molecular Profiling; Myelogenous; Myeloid Cells; Natural Immunity; Nature; Novavax COVID-19 vaccine; Peripheral Blood Mononuclear Cell; Pfizer-BioNTech COVID-19 vaccine; Plasma; Population; Predisposition; RNA vaccine; Rabies; Rabies Vaccines; Rabies virus; Recombinants; Reporting; Resistance; Role; Sampling; Saponins; Secondary Immunization; Serum; South Africa; South African; Special Population; System; Vaccinated; Vaccination; Vaccines; Viral; Virus; Work; ZIKA; adaptive immune response; adaptive immunity; antigen-specific T cells; biological systems; cytokine; epigenomics; gut microbiota; immunogenicity; immunoregulation; imprint; influenza virus vaccine; innate immune mechanisms; insight; lymph nodes; metabolomics; microbiome; microbiota; monocyte; multiple omics; novel; pandemic influenza; response; seasonal influenza; transcriptomics; vaccine development; vaccinology; young adult

ABSTRACT – Project 1 In the current proposal, we will use systems biological approaches 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 allergies is unknown. It is conceivable that in such populations, a predisposition towards Th2 responses, could alter the quality of the immune response. 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 innate immune mechanisms stimulated by the saponin-based Matrix-M adjuvant. We will analyze samples collected from a Novavax sponsored clinical trial of their investigational subunit COVID-19 vaccine in South African adults. 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 issues will be addressed in the following specific aims: Aim 1: Systems biological assessment of innate responses to vaccination against COVID-19. Sub-aim 1a: Multi-omics assessment of innate responses to the BNT162b2 mRNA vaccine in atopic vs. healthy adults. Sub-aim 1b: Multi-omics assessment of innate responses to the Novavax COVID-19 vaccine. Aim 2: Systems biological assessment of the impact of the microbiota on innate immunity to rabies vaccination.

摘要 – 项目 1 在当前的提案中，我们将使用系统生物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，该疫苗利用新颖的平台 (mRNA) 或佐剂（Novavax 疫苗中使用的 Matrix M）。第二个问题涉及到的角色 微生物组对疫苗免疫的影响。关于第一个问题，尽管新冠肺炎疫情发展迅速， 19 种疫苗，人们对它们诱导先天性和 适应性反应。此外，mRNA 疫苗诱导的免疫反应的本质是特殊的。 诸如严重过敏人群之类的人群尚不清楚。可以想象，在这样的人群中， Th2 反应的倾向可能会改变免疫反应的质量。有趣的是， 据报道，患有特应性过敏的个体对疫苗接种产生了罕见但严重的过敏反应 背景。因此，我们将评估特应性受试者与健康受试者对 BNT162b2 疫苗的免疫力。在 以 Novavax 开发的 Matrix-M 佐剂重组 COVID-19 疫苗为例， 对基于皂苷的 Matrix-M 佐剂刺激的先天免疫机制缺乏了解。 我们将分析从 Novavax 赞助的研究亚单位临床试验中收集的样本 南非成年人接种 COVID-19 疫苗。 该提案的第二个主题集中于微生物组对免疫力的影响 健康成年人接种疫苗。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疫苗接种免疫反应中的重要作用 季节性流感疫苗。然而，成人对季节性流感疫苗的免疫反应 代表由于之前接触过流感而做出的召回反应。微生物组对的影响 初级免疫反应，例如对狂犬病疫苗接种的反应，尚不清楚。这些问题将会 解决以下具体目标： 目标 1：对 COVID-19 疫苗接种的先天反应进行系统生物学评估。 子目标 1a：特应性与非过敏性人群对 BNT162b2 mRNA 疫苗先天反应的多组学评估 健康的成年人。 子目标 1b：对 Novavax COVID-19 疫苗先天反应的多组学评估。 目标 2：对微生物群对狂犬病先天免疫影响的系统生物学评估 疫苗接种。