Antibody display libraries for precision screening of antibody immune responses to SARS-CoV-2
用于精确筛选针对 SARS-CoV-2 的抗体免疫反应的抗体展示文库
基本信息
- 批准号:10199286
- 负责人:
- 金额:$ 25.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAcute Lung InjuryAddressAffinityAntibodiesAntibody RepertoireAntibody ResponseAntibody-Dependent EnhancementAntigensAntiviral AgentsB-LymphocytesBindingCOVID-19COVID-19 pandemicCardiovascular DiseasesCell SurvivalCellsCharacteristicsChromosomesClinicalDNADevelopmentDiabetes MellitusDiseaseEndosomesEnvironmentEpitope MappingEpitopesEquilibriumFluorescence-Activated Cell SortingFollow-Up StudiesGenesGeneticHumanImmuneImmune responseImmunityImmunologic MarkersIn VitroIndividualInfectionInterventionLibrariesLightLinkLung diseasesMapsMedicalMessenger RNAMiddle East Respiratory Syndrome CoronavirusMolecularMonoclonal AntibodiesN-terminalNucleocapsid ProteinsObesityPathway interactionsPatientsPharmaceutical PreparationsPlasmaPopulationPrevention therapyProceduresPropertyProtein ConformationProteinsRecoveryRespiratory distressRiskRoleSARS coronavirusSamplingSerologicalSevere Acute Respiratory SyndromeSeveritiesSeverity of illnessSorting - Cell MovementSpeedStructureSymptomsTechniquesTechnologyVaccinesViralViral AntibodiesViral ProteinsVirusYeastsantibody librariesbaseburden of illnesscohortcoronavirus diseasecostdata miningdrug candidatedrug developmentdrug discoveryexperimental studyhigh riskimprovedinsightlarge scale datalung injurymedical countermeasuremolecular scalemortalityneutralizing antibodynext generation sequencingpandemic diseasepatient populationpersonalized screeningpotential biomarkerpreventreceptor bindingresponsescreeningsingle cell analysissmall molecule
项目摘要
PROJECT SUMMARY/ABSTRACT
This project will determine the antibody-based immune features in COVID-19 patients to accelerate the
development of new medical interventions. SARS-CoV-2 causes asymptomatic or mild disease in many
individuals, demonstrating that an effective human immune response can fully prevent disease. However, it
remains unclear what immune response features are associated with protection from disease. To address this
question, here we will analyze comprehensive antibody immune responses in COVID-19 patients and determine
how the molecular features of antibody immunity correlate with COVID-19 symptom severity.
First, we will immortalize antibody immune libraries from COVID-19 patient cohorts into yeast display libraries
for comprehensive in vitro functional screening. B cell samples from COVID-19 patients will be isolated and
emulsified as single cells for native antibody DNA recovery, and antibody genes will be transformed into a yeast
Fab display platform for repertoire-scale antibody functional analyses. Antibodies will be screened for binding to
the SARS-CoV-2 spike trimer, a dominant neutralization target, and also for inhibition of ACE2 binding to map
neutralizing antibodies in human immune responses.
We will also mine our renewable antibody immune libraries for broader features that may correlate with
COVID-19 disease severity. We will investigate antibodies targeting broad SARS-CoV-2 antigens and epitopes,
including multiple epitopes on the spike trimer protein (such as the receptor binding domain, RBD, the N terminal
domain, NTD, and the S1 region) and internal viral proteins (e.g., nucleocapsid protein). We will also map the
molecular features of single B cell responses (e.g. affinity, competition-based epitope mapping, and differential
binding to different spike protein conformations) to comprehensively track anti-SARS-CoV-2 molecular immunity
in a human cohort. We will analyze the genetic features of each antibody clone to help elucidate the balance of
neutralizing vs. non-neutralizing antibodies as potential disease correlates.
Finally, we will perform large-scale data mining of the antibody repertoires from each patient population to
identify key molecular features that may distinguish mild and severe SARS-CoV-2 infections. These new
molecular-scale correlates and potential biomarkers will improve basic and clinical understanding to advance
COVID-19 preventions and therapies. We seek to reveal critical immune-based biomarkers of COVID-19
diseases severity and identify new potent antibody drug candidates to treat and prevent COVID-19.
项目总结/文摘
项目成果
期刊论文数量(0)
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Brandon James DeKosky其他文献
Brandon James DeKosky的其他文献
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{{ truncateString('Brandon James DeKosky', 18)}}的其他基金
Potent broadly neutralizing antibody development against the HIV-1 fusion peptide epitope
针对 HIV-1 融合肽表位的强效广泛中和抗体的开发
- 批准号:
10838825 - 财政年份:2023
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$ 25.93万 - 项目类别:
Comprehensive analysis of human adaptive immune receptors to elucidate correlates of Epstein-Barr virus disease suppression
全面分析人类适应性免疫受体以阐明 Epstein-Barr 病毒疾病抑制的相关性
- 批准号:
10619219 - 财政年份:2022
- 资助金额:
$ 25.93万 - 项目类别:
Antibody display libraries for precision screening of antibody immune responses to SARS-CoV-2
用于精确筛选针对 SARS-CoV-2 的抗体免疫反应的抗体展示文库
- 批准号:
10649740 - 财政年份:2022
- 资助金额:
$ 25.93万 - 项目类别:
Rapid antibody screening systems to identify and engineer antiviral protection
用于识别和设计抗病毒保护的快速抗体筛选系统
- 批准号:
10353350 - 财政年份:2022
- 资助金额:
$ 25.93万 - 项目类别:
Rapid antibody screening systems to identify and engineer antiviral protection
用于识别和设计抗病毒保护的快速抗体筛选系统
- 批准号:
10818691 - 财政年份:2022
- 资助金额:
$ 25.93万 - 项目类别:
Rapid antibody screening systems to identify and engineer antiviral protection
用于识别和设计抗病毒保护的快速抗体筛选系统
- 批准号:
10580028 - 财政年份:2022
- 资助金额:
$ 25.93万 - 项目类别:
Comprehensive analysis of human adaptive immune receptors to elucidate correlates of Epstein-Barr virus disease suppression
全面分析人类适应性免疫受体以阐明 Epstein-Barr 病毒疾病抑制的相关性
- 批准号:
9212615 - 财政年份:2016
- 资助金额:
$ 25.93万 - 项目类别:
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