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: 10879820
• 负责人: BALI PULENDRAN
• 金额: $ 22.32万
• 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/10879820
• 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; Immunologic Stimulation; Immunology; Individual; Influenza; 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; Recommendation; 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; Vaccination; Vaccines; Validation; Work; adaptive immunity; antigen-specific T cells; biological systems; cytokine; data integration; data management; data submission; epigenomics; human subject; immunoregulation; 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 – 总体组成部分 在当前的提案中，我们将使用系统疫苗学方法来解决两个基本问题： 第一个问题涉及利用新平台的 COVID-19 疫苗的免疫学。 （mRNA）或佐剂（Novavax 疫苗中使用的 Matrix M）第二个问题与佐剂的作用有关。 关于第一个问题，尽管新冠病毒发展迅速，但微生物组对疫苗免疫的影响。 19 种疫苗，人们对它们诱导先天性和 此外，mRNA 疫苗诱导的免疫反应具有特殊的性质。 诸如患有严重过敏性疾病的人群尚不清楚。 有特应性背景的个体对疫苗接种产生罕见但严重的过敏反应。 评估 Matrix-M 受试者与健康受试者对 BNT162b2 疫苗特应性的免疫力。 Novavax 开发的佐剂重组 COVID-19 疫苗，目前仍缺乏了解 基于皂苷的 Matrix-M 佐剂刺激的免疫机制我们将分析收集的样本。 来自 Novavax 赞助的南非临床试验。 该提案的第二个主题集中于微生物组对免疫力的影响 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产生的召回反应。 初级免疫反应，例如对狂犬病疫苗接种的反应，尚不清楚。 这两个问题将在以下高度协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 该项目中确定的特征将与抗原特异性 T 细胞和 B 细胞相关联。 项目 2 (PI Davis) 和项目 3 (PI Boyd) 中评估的响应将分别进行深入的评估。 抗原特异性 T 细胞对疫苗接种反应的动态分析项目 3（PI Boyd；Co-I）。 Nadeau）将深入分析抗原特异性 B 细胞对 这三个项目将由 4 个核心人员协助。 HIPC-斯坦福中心的协调工作将确保 所有研究中人类受试者的招募和临床特征的标准化方法； 数据管理和分析核心（PI Khatri）将提供生物信息学专业知识，以及人类 免疫监测核心（PI Holden）将通过提供免疫监测检测来支持这些项目。

项目成果

Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation.

含有 Toll 样受体激动剂的皂苷纳米颗粒佐剂可改善疫苗免疫调节。

• 发表时间: 2023-12-31
• 作者: Ou, Ben S;Baillet, Julie;Filsinger Interrante, Maria Victoria;Adamska, Julia Z;Zhou, Xueting;Saouaf, Olivia;Yan, Jerry;Klich, John;Jons, Carolyn K;Meany, Emily;Valdez, Adian S;Carter, Lauren;Pulendran, Bali;King, Neil P;Appel, Eric
• 通讯作者: Appel, Eric

Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2.

使用 AS03 佐剂的 SARS-CoV-2 单价亚单位疫苗对猕猴进行免疫接种而产生的极其有效的泛 sarbecovirus 中和抗体。

• 发表时间: 2023-01-20
• 作者: Feng, Yupeng;Yuan, Meng;Powers, John M;Hu, Mengyun;Munt, Jennifer E;Arunachalam, Prabhu S;Leist, Sarah R;Bellusci, Lorenza;Adams, Lily E;Sundaramurthy, Sumana;Shirreff, Lisa M;Mallory, Michael L;Scooby, Trevor D;Moreno, Alberto;O'Hagan, Dere
• 通讯作者: O'Hagan, Dere

Designing spatial and temporal control of vaccine responses.

设计疫苗反应的空间和时间控制。

• 发表时间: 2022
• 作者: Roth, Gillie A;Picece, Vittoria C T M;Ou, Ben S;Luo, Wei;Pulendran, Bali;Appel, Eric A
• 通讯作者: Appel, Eric A

Direct comparison of antibody responses to four SARS-CoV-2 vaccines in Mongolia.

蒙古对四种 SARS-CoV-2 疫苗的抗体反应的直接比较。

• 发表时间: 2021-12-08
• 影响因子: 30.3
• 作者: Dashdorj, Naranjargal J;Wirz, Oliver F;Röltgen, Katharina;Haraguchi, Emily;Buzzanco 3rd, Anthony S;Sibai, Mamdouh;Wang, Hannah;Miller, Jacob A;Solis, Daniel;Sahoo, Malaya K;Arunachalam, Prabhu S;Lee, Alexandra S;Shah, Mihir M;Liu, James;Byam
• 通讯作者: Byam

Progress in vaccine development for infectious diseases-a Keystone Symposia report.

传染病疫苗开发进展——Keystone Symposia 报告。

• 发表时间: 2023-06
• 影响因子: 5.2
• 作者: Cable, Jennifer;Graham, Barney S;Koup, Richard A;Seder, Robert A;Karikó, Katalin;Pardi, Norbert;Barouch, Dan H;Sharma, Bhawna;Rauch, Susanne;Nachbagauer, Raffael;Forsell, Mattias N E;Schotsaert, Michael;Ellebedy, Ali H;Loré, Karin;Irvine, Da
• 通讯作者: Irvine, Da