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 在当前的建议中，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 诸如严重过敏的人群尚不清楚。可以想象，在这样的人群中 对Th2反应的易感性可能会改变免疫反应的质量。有趣的是， 有报道称疫苗接种罕见但严重的过敏反应 背景。因此，我们将评估对BNT162B2疫苗与健康受试者的免疫力。在 novavax开发的基质-M调整后的重组covid-19疫苗的情况，有一个 对基于皂苷的基质-M刺激的对先天免疫机制的理解很少。 我们将分析从Novavax赞助的研究子功能的临床试验中收集的样品 南非成年人的Covid-19疫苗。 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。这些问题将是 在以下具体目的中解决： 目的1：系统生物学评估对Covid-19的先天反应对疫苗接种的反应。 Sub-aim 1A：对ATOPIC VS中BNT162B2 mRNA疫苗的先天反应评估。 健康的成年人。 Sub-Aim 1B：对Novavax Covid-19疫苗的先天反应的多摩学评估。 目标2：系统生物学评估微生物群对狂犬病先天免疫的影响 疫苗接种。