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 在目前的提案中，我们将使用系统生物学方法来解决以下两个基本问题 疫苗学。第一个问题涉及新冠肺炎疫苗的免疫学，这种疫苗利用了新的平台 (信使核糖核酸)或佐剂(Novavax疫苗中使用的基质M)。第二个问题是与 微生物组对疫苗免疫的影响。关于第一个问题，尽管COVID发展迅速-- 19种疫苗，对它们诱导天生和 适应性反应。此外，本研究还对基因疫苗诱导的免疫应答的性质进行了初步探讨。 像那些严重过敏的人这样的人群是未知的。可以想象，在这样的人群中， 对Th2反应的易感性，可以改变免疫反应的质量。有趣的是， 有报道称，在患有特应症的个体中，接种疫苗发生了罕见但严重的过敏反应。 背景资料。因此，我们将评估BNT162b2特应性疫苗与健康受试者的免疫力。在……里面 诺华公司开发的矩阵-M佐剂重组新冠肺炎疫苗的案例中，存在 缺乏对皂苷类基质-M佐剂刺激的先天免疫机制的了解。 我们将分析从Novavax赞助的他们的研究亚单位的临床试验中收集的样本 南非成人接种新冠肺炎疫苗。 提案的第二个主题是微生物群对免疫系统的影响。 在健康的成年人中接种疫苗。我们最近关于抗生素驱动的微生物区系消融的工作已经 强调了微生物群在调节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 代表召回反应，因为之前接触过流感。微生物群对细菌的影响 初级免疫反应，如对狂犬病疫苗接种的反应，尚不清楚。这些问题将是 具体目标如下： 目的1：新冠肺炎疫苗先天免疫反应的系统生物学评价。 次目标1a：特应性和非特应性患者对BNT162b2基因疫苗先天反应的多组学评估。 健康的成年人。 分目标1b：对新药新冠肺炎疫苗先天反应的多组学评估。 目标2：微生物区系对狂犬病先天免疫影响的系统生物学评估 接种疫苗。