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， （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 如那些严重过敏的人群是未知的。可以想象，在这样的人群中， 对Th 2应答的易感性，可以改变免疫应答的质量。有趣的是， 有报道称，在特应性免疫缺陷的个体中， 背景因此，我们将评估与健康受试者相比，对BNT 162 b2特应性疫苗的免疫力。在 在Novavax开发的Matrix-M佐剂重组COVID-19疫苗的情况下， 缺乏对基于皂苷的Matrix-M佐剂刺激的先天免疫机制的理解。 我们将分析从Novavax申办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。这些问题将 具体目标如下： 目的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：多组学评估特应性vs. 健康成人 子目标1b：Novavax COVID-19疫苗先天反应的多组学评估。 目的2：系统生物学评估微生物群对狂犬病先天免疫的影响 预防针