COVID-19: Significance of Fc properties and functions in antibody responses against SARS-CoV-2
COVID-19:Fc 特性和功能在针对 SARS-CoV-2 的抗体反应中的重要性
基本信息
- 批准号:10365140
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAddressAdvanced DevelopmentAffectAffinityAnimalsAntibodiesAntibody ResponseAntigensBindingBiologyBloodCOVID-19COVID-19 diagnosticCOVID-19 interventionCOVID-19 pandemicCOVID-19 patientCOVID-19 therapeuticsCOVID-19 vaccineCaringCellsCessation of lifeChinaChitraCommunicable DiseasesComplementComplement 1qDNA VaccinesDataDeath RecordsDepositionDetectionDevelopmentDiagnosticDiseaseDisease OutbreaksDisease OutcomeElderlyEmergency SituationEmployeeFailureGlycoproteinsGoalsHIVHospitalsHumanIgG1Immunoglobulin AImmunoglobulin GImmunoglobulin IsotypesImmunoglobulin MImmunologyIndividualInfectionInflammatoryLeadLiquid substanceMacaca mulattaMass Spectrum AnalysisMeasuresMediatingMedical centerMucous MembraneMyeloid CellsPatientsPhagocytosisPlasmaPolysaccharidesPopulationPositioning AttributeProductionPropertyProxyPublishingRNA vaccineReportingResearchRisk FactorsRoleSARS-CoV-2 antibodySARS-CoV-2 infectionSARS-CoV-2 spike proteinSalivaSignal TransductionSpecialistSpecimenStructureSymptomsTestingTimeVaccinationVaccineeVaccinesVeteransViralVirionVirusVulnerable PopulationsWorkantibody-dependent cellular phagocytosisbaseconvalescent plasmacytokinecytotoxicityexperienceglycosylationhigh riskimprovedmalemedical schoolsmucosal siteneutralizing antibodyneutrophilnovel coronaviruspandemic diseasepreclinical studyprophylacticreceptor bindingresponsesaliva samplesevere COVID-19vector
项目摘要
Project Summary/Abstract
The COVID-19 pandemic, which is caused by SARS-CoV-2, a novel coronavirus first detected in
November-December 2019, has inflicted millions of deaths worldwide. In the US, the outbreak is affecting
millions of lives. The VA hospitals, including the James J. Peters VA Medical Center (JJP VAMC) in the Bronx,
NY, have responded promptly to provide care to Veterans and employees. Veterans are typically older than the
general US population, making them highly susceptible to severe disease. COVID-19 vaccines are also
distributed initially to the elderly and other high-risk individuals. This provides the VA a unique opportunity to
study SARS-CoV-2 infection and vaccination in the most vulnerable individuals.
This VA Merit application proposes to investigate the protective role of antibodies (Abs) elicited against
the SARS-CoV-2 spike protein and its receptor-binding domain (RBD) following vaccination or infection. In
particular, we will examine the Ab Fc properties and functions that are not well understood and the Abs that are
present in blood and in saliva as a proxy of Abs at the mucosal site of virus entry. The proposed study is built
upon our published and preliminary results showing the detection of different immunoglobulin (Ig) isotypes
against SARS-CoV-2 spike and RBD in saliva vs plasma of convalescent COVID-19 patients and vaccine
recipients. Interestingly, our preliminary data indicate a lack of correlation of spike-specific Ig isotypes in saliva
vs plasma from infected and vaccinated subjects. The data further show the binding of C1q, the first
component in the classical complement cascade, to Abs from both infected and vaccinated subjects. Notably,
the C1q binding activities of Abs in saliva vs plasma correlated poorly, offering the initial evidence for
differential Fc functions of mucosal vs circulating anti-spike Abs elicited by infection and vaccination.
To investigate further the Fc properties and functions of Abs against SARS-CoV-2, we hypothesize
that Fc isotype and glycosylation are the key determinants of Fc-dependent Ab functions in protection
against COVID-19. A research team that include research specialists with expertise in Abs and viral
immunology (PI: Catarina Hioe at JJP VAMC; collaborators: Susan Zolla-Pazner, Chitra Upadhyay, Ray
Alvarez at Mount Sinai School of Medicine/MSSM), an expert in mass spectrometry and glycan biology (Hui
Zhang at Johns Hopkins Univ), and an infectious disease clinician (Co-I: Juan Bandres at JJP VAMC) will work
together to test this hypothesis. We will leverage our extensive expertise in Abs against HIV envelope
glycoprotein and our experience investigating Ab responses against SARS-CoV-2 in the past year. In Aim 1,
we will collect longitudinal plasma and saliva samples to determine the isotypes and durability of Abs against
spike and RBD in different bodily fluids of ambulatory and hospitalized COVID-19 patients and healthy
uninfected recipients of COVID-19 RNA vaccines. Aim 2 will evaluate the glycan structures on the Fc regions
of Abs against spike from SARS-CoV-2-infected and vaccinated subjects. Aim 3 will assess the Fc-mediated
activities that these Abs mediate to destroy virus particles and virus-infected cells, i.e. complement
binding/activation and FcɣR-mediated signaling, cytotoxicity, and phagocytosis. Abs of different Ig isotypes and
with experimentally modified Fc glycans will also be examined for their Fc-dependent activities. The proposed
study will produce data critical to advance the development of improved Ab-based arsenals for diagnostics,
prophylactics, and therapeutics against COVID-19.
项目总结/文摘
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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Catarina E Hioe其他文献
Catarina E Hioe的其他文献
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{{ truncateString('Catarina E Hioe', 18)}}的其他基金
COVID-19: Significance of Fc properties and functions in antibody responses against SARS-CoV-2
COVID-19:Fc 特性和功能在针对 SARS-CoV-2 的抗体反应中的重要性
- 批准号:
10609822 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Biologic consequences of HIV-1 interaction with bacteria
HIV-1 与细菌相互作用的生物学后果
- 批准号:
10263148 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Harnessing Abs specific for immunogenic and conserved Env epitopes to protect against HIV
利用免疫原性和保守的 Env 表位特异性抗体来预防 HIV
- 批准号:
10401312 - 财政年份:2018
- 资助金额:
-- - 项目类别:
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