Immunological responses to pan-CoV vaccines
对泛冠状病毒疫苗的免疫反应
基本信息
- 批准号:10841734
- 负责人:
- 金额:$ 155.82万
- 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-nCoVAffinityAnimal ModelAnimalsAntibodiesAntibody SpecificityAntigensB-LymphocytesCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCOVID-19COVID-19 patientCell MaturationCellsCellular ImmunityCohort StudiesCollaborationsCollectionCoronavirusCoronavirus InfectionsCross ReactionsCytotoxic T-LymphocytesDataDevelopmentDiseaseEnsureEpitopesEvaluationFundingFunding OpportunitiesGenerationsGoalsHeadHumanImmuneImmune responseImmune systemImmunityImmunizeImmunodominant EpitopesImmunoglobulinsImmunologic TestsInfectionInfluenzaLaboratoriesLongitudinal cohort studyMediatingMemory B-LymphocyteMethodsMiddle East Respiratory Syndrome CoronavirusMonoclonal AntibodiesMusOutcomePersonsPhase I Clinical TrialsPhenotypePlasma CellsPolysaccharidesProteinsReactionResearch PersonnelResearch Project GrantsSARS coronavirusSamplingStructure of germinal center of lymph nodeSystemT cell responseT-LymphocyteT-Lymphocyte EpitopesTestingVaccinatedVaccine AntigenVaccinesVariantViraladaptive immune responsecandidate validationcell killingcoronavirus vaccinecross immunitycross reactivitycytotoxicdesignhigh throughput analysishuman coronavirushuman monoclonal antibodieslong term memorynovelnovel coronavirusnovel vaccinespost SARS-CoV-2 infectionpre-clinicalprogramsreconstructionresponsesingle cell technologystemuniversal coronavirus vaccinevaccine candidatevaccine developmentvaccine platform
项目摘要
Summary
The pan-coronavirus vaccine (PanCoVac) consortium will develop novel coronavirus vaccines that can
provide protection against a range of coronaviruses. Research Project 1 (RP1, ‘Design and evaluation of pan-
CoV vaccines’) will develop novel coronavirus antigens and test them in pre-clinical animal models. Research
Project, RP2, will test the ‘Immunological Responses to pan-CoV vaccines’, including a detailed analysis of
B and T cell responses in mice immunized with antigens developed in RP1 and formulated into a vaccine
platform. In Aim 1 (‘Provide a panel of well-characterized antibodies cross-reacting or specific to various
coronavirus strains’), human monoclonal antibodies (mAbs) cloned from the B cells from COVID-19 patients
will be generated and characterized for activity against various coronaviruses. The functional and structural
characterization will be carried out in collaboration with investigators in RP1. The characterized mAbs will be
provided to RP1 to test novel antigens. The goal is to identify novel antigens that maintain key cross-reactive
epitopes while strain-specific immunodominant epitopes are lost. In Aim 2 (‘Analysis of B cell immunity cross-
reactive to SARS-CoV-2 and other coronavirus strains’), “Ig-omics”, i.e., single-cell technologies allowing
high-throughput analysis of B cell responses, phenotypes, immunoglobulin (Ig) repertoires and mAbs that react
to various coronaviruses (developed by one of the RP2 investigators) will be utilized for characterizing B cell-
mediated immunity and mAb specificity induced by the candidate vaccine antigens. These data will be compared
with results from a human cohort study (funded through a different mechanism) to identify vaccine candidates
that generate a broad B cell response and stimulate affinity maturation in germinal centers and the generation
of long-term memory B cells and plasma cells. In Aim 3 (‘Analysis of T cell immunity cross-reactive to SARS-
CoV-2 and other coronavirus strains’), we will test the ability of novel vaccine candidates to elicit responses
to cross-reactive CD4 and CD8 epitopes. In particular, novel methods based on T cell repertoire sequencing will
be used to characterize epitope-specific responses that are cross-reactive between SARS-CoV-2 and other
human coronaviruses, and those responses that are SARS-CoV-2 specific. Using data from ongoing longitudinal
cohort study of SARS-CoV-2-infected people (funded through a different mechanism), we will be able to identify
naïve and baseline cross-reactive T cell responses that expand after SARS-CoV-2 infection. These data will be
compared with the T cell responses in mice vaccinated with the novel vaccine candidates. Overall, these data
will allow an in-depth comparison of B and T cell responses between vaccinated animals and human COVID-
19 samples in order to refine vaccine candidates to be more cross-reactive.
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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YOSHIHIRO KAWAOKA其他文献
YOSHIHIRO KAWAOKA的其他文献
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{{ truncateString('YOSHIHIRO KAWAOKA', 18)}}的其他基金
Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
- 批准号:
10821572 - 财政年份:2023
- 资助金额:
$ 155.82万 - 项目类别:
Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
- 批准号:
10359831 - 财政年份:2021
- 资助金额:
$ 155.82万 - 项目类别:
Development of broadly-protective vaccines for influenza B viruses
开发针对乙型流感病毒的广泛保护性疫苗
- 批准号:
10206685 - 财政年份:2021
- 资助金额:
$ 155.82万 - 项目类别:
COVID-19 comorbidity studies in Syrian hamster models
叙利亚仓鼠模型中的 COVID-19 合并症研究
- 批准号:
10450889 - 财政年份:2021
- 资助金额:
$ 155.82万 - 项目类别:
PanCorVac (Center for Pan-Coronavirus Vaccine Development)
PanCorVac(泛冠状病毒疫苗开发中心)
- 批准号:
10841731 - 财政年份:2021
- 资助金额:
$ 155.82万 - 项目类别:
COVID-19 comorbidity studies in Syrian hamster models
叙利亚仓鼠模型中的 COVID-19 合并症研究
- 批准号:
10285154 - 财政年份:2021
- 资助金额:
$ 155.82万 - 项目类别:
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