Features of Broad T Cell Coronavirus Immunity

广泛 T 细胞冠状病毒免疫的特点

基本信息

  • 批准号:
    10842889
  • 负责人:
  • 金额:
    $ 198.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-16 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project 2 Summary Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has quickly become a global health crisis of epic proportion. This pandemic, along with the SARS-CoV epidemic of 2002 and MERS-CoV epidemic of 2012, highlights the tremendously dangerous ongoing threat to humanity posed by emerging human-tropic coronaviruses that are transitioning from bats and other wildlife species into humans. Thus, while early vaccines for SARS-CoV-2 have already demonstrated remarkable efficacy, next generation vaccines should deliver broad protection against a wide spectrum of coronaviruses as well as improved robustness against newly emerging SARS-CoV-2 variants that threaten immune escape. The overall goal of this program is to design a pan-coronavirus vaccine strategy by coupling key immunological information regarding the B cell and antibody response (Project 1) with the T cell response (Project 2) from SARS-CoV-2 infection and vaccination to advanced structural design and vaccine delivery strategies (Project 3). This synergistic program seeks to design a protective, durable vaccine able to induce immunity across a spectrum of human as well as zoonotic coronaviruses. To do so will require a better understanding of the immunodominant epitopes targeted by B cells and T cells as well as the extent of cross-reactivity these responses have against conserved epitopes across coronavirus species. For T cells, which is the focus of Project 2, durable pan-coronavirus immunity will likely require robust cross-reactive responses by multiple effector subsets, including T helper type 1 (TH1), T follicular helper (TFH), and cytotoxic T cells (CTL) generated in both circulating and respiratory mucosal tissue-resident compartments. The overall goal of this project is to apply the knowledge gained from our studies of SARS-CoV-2-specific T cells in convalescent COVID-19 patients and vaccinees as well as innovative new experimental designs in mouse models to inform the design of vaccine immunogens by Project 3 that will maximize cross-reactive, yet durable and functionally diverse T cell immunity that will protect against multiple coronaviruses. We hypothesize that the quality of T cell immunity to coronaviruses varies by epitope and that pan-coronavirus vaccine design should incorporate epitopes based collectively on immunodominance, functional diversity, and breadth of cross-reactivity. The studies in this project will identify the best epitopes for this purpose. Specifically, we propose: 1) To identify SARS-CoV-2 CD4+ T cell epitopes from studies of convalescent COVID-19 patients and vaccinees that exhibit the greatest extent of immunodominance, durability, and cross-reactivity; 2) Evaluate the efficacy of cross-reactive CD4+ T cell epitopes in novel vaccine immunogens to induce protective immune responses in animal models; and 3) Discover new MHC class I epitopes using innovative screening technologies and evaluate their ability to generate protective CD8+ T cell responses in mice.
项目二总结

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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ANDREW D LUSTER其他文献

ANDREW D LUSTER的其他文献

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{{ truncateString('ANDREW D LUSTER', 18)}}的其他基金

Allergen-specific lung-resident Tregs in asthma: Targetable suppressors of resident memory Th2 cells
哮喘中过敏原特异性肺常驻 Tregs:常驻记忆 Th2 细胞的靶向抑制因子
  • 批准号:
    10563192
  • 财政年份:
    2022
  • 资助金额:
    $ 198.74万
  • 项目类别:
Allergen-specific lung-resident Tregs in asthma: Targetable suppressors of resident memory Th2 cells
哮喘中过敏原特异性肺常驻 Tregs:常驻记忆 Th2 细胞的靶向抑制因子
  • 批准号:
    10418189
  • 财政年份:
    2022
  • 资助金额:
    $ 198.74万
  • 项目类别:
Features of Broad T Cell Coronavirus Immunity
广泛 T 细胞冠状病毒免疫的特点
  • 批准号:
    10328120
  • 财政年份:
    2021
  • 资助金额:
    $ 198.74万
  • 项目类别:
The CXCR3 Chemokine System in Cancer Immunotherapy
癌症免疫治疗中的 CXCR3 趋化因子系统
  • 批准号:
    10053710
  • 财政年份:
    2016
  • 资助金额:
    $ 198.74万
  • 项目类别:
2014 Chemotactic Cytokines Gordon Research Conference and Gordon Research Seminar
2014年趋化细胞因子戈登研究大会暨戈登研究研讨会
  • 批准号:
    8708388
  • 财政年份:
    2014
  • 资助金额:
    $ 198.74万
  • 项目类别:
2012 Chemotactic Cytokines Gordon Research Conference & Gordon Research Seminar
2012年趋化细胞因子戈登研究会议
  • 批准号:
    8307657
  • 财政年份:
    2012
  • 资助金额:
    $ 198.74万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8196493
  • 财政年份:
    2011
  • 资助金额:
    $ 198.74万
  • 项目类别:
Linking allergen-specific T cell effector and regulatory responses to asthma
将过敏原特异性 T 细胞效应器与哮喘调节反应联系起来
  • 批准号:
    8196484
  • 财政年份:
    2011
  • 资助金额:
    $ 198.74万
  • 项目类别:
T cell effector and regulatory mechanisms in asthma and food allergy
哮喘和食物过敏中的 T 细胞效应和调节机制
  • 批准号:
    8707948
  • 财政年份:
    2011
  • 资助金额:
    $ 198.74万
  • 项目类别:
T cell effector and regulatory mechanisms in asthma and food allergy
哮喘和食物过敏中的 T 细胞效应和调节机制
  • 批准号:
    8165321
  • 财政年份:
    2011
  • 资助金额:
    $ 198.74万
  • 项目类别:

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非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
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