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
- 来源:
- 关键词:2019-nCoVAllelesAnimal ModelAntibody ResponseAntigensB-LymphocytesBindingBiological AssayC57BL/6 MouseCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCOVID-19COVID-19 patientCOVID-19 vaccineCell LineChiropteraCoronavirusCouplingCytotoxic T-LymphocytesDangerousnessDevelopmentEpidemicEpitopesExhibitsExperimental DesignsFrequenciesGenerationsGoalsHumanHumanitiesImmuneImmune responseImmunityImmunodominant EpitopesImmunologic MemoryImmunologicsIndividualInfectionIntramuscularK-18 conjugateKnowledgeLibrariesLinkMHC Class I GenesMHC binding peptideMemory B-LymphocyteMethodsMiddle East Respiratory SyndromeMiddle East Respiratory Syndrome CoronavirusMucous MembraneMusPatientsPeptide/MHC ComplexPeptidesPhenotypePhysical assessmentProteinsResearch PersonnelRespiratory MucosaRouteSARS coronavirusSARS-CoV-2 infectionSARS-CoV-2 variantSevere Acute Respiratory SyndromeSomatic MutationStructure of germinal center of lymph nodeT cell responseT-LymphocyteT-Lymphocyte EpitopesTechnologyTestingTransgenic MiceVaccinatedVaccinationVaccine DesignVaccineeVaccinesbetacoronavirus vaccinecross reactivitydesignefficacy evaluationglobal healthhuman coronavirushuman subjectimprovedinnovationmouse modelnovel vaccinespandemic diseaseprogramsresponsescreeningtissue resident memory T celluniversal coronavirus vaccinevaccine candidatevaccine deliveryvaccine efficacyvaccine strategyzoonotic coronavirus
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)
科研奖励数量(0)
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
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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
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8307657 - 财政年份:2012
- 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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