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
基本信息
- 批准号:10580028
- 负责人:
- 金额:$ 21.82万
- 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:2022-02-25 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAccelerationAddressAntibodiesAntibody ResponseAntibody-Dependent EnhancementAntibody-mediated protectionAntigensAreaB-LymphocytesBindingBiological AssayBiological ModelsCD209 geneCOVID-19 pandemicCOVID-19 patientCellsCellular AssayClinicalClinical ResearchCollaborationsCommunicable DiseasesConsumptionCustomData CollectionDengue VaccineDengue VirusDevelopmentDirected Molecular EvolutionDisease OutbreaksEngineeringEnsureEpitopesFailureFlavivirusFlow CytometryFutureGenesHumanImmuneImmune responseImmunityImmunologic MemoryImmunologyIn VitroInfectionInterventionLightLinkMapsMedicalMethodsModelingMolecularMutationNaturePatientsPharmaceutical PreparationsPharmacotherapyPopulationProductivityPropertyProxyRecombinantsRecording of previous eventsRecoveryResistanceSARS-CoV-2 antibodySARS-CoV-2 variantSamplingSystemTechniquesTechnologyTherapeutic antibodiesTimeVaccinationVaccine DesignVaccine TherapyVaccineeVaccinesVariantViralViral AntibodiesViral VaccinesVirulenceVirusVirus DiseasesWorkWritingYellow fever virusadaptive immune responseantibody engineeringantibody librariesantigen bindingantiviral drug developmentbetacoronaviruscombatcross reactivitydesigndrug developmenthigh throughput screeningimprovedinnovationinsightmedical countermeasuremultidisciplinaryneutralizing antibodyneutralizing monoclonal antibodiesnext generation sequencingpandemic diseaseparticlepressurerapid techniquescreeningsuccessvaccine developmentviral pandemic
项目摘要
PROJECT SUMMARY
A detailed understanding of molecular and cellular adaptive immune responses is critical to accelerate
progress in human immunology and drug development. However, available technologies for analyzing antiviral
neutralizing antibody responses are slow and impractical for large-scale clinical sample analysis, and can provide
limited information on the scope of neutralizing antibody features in human immunity. Importantly, current
methods are also unable to engineer antibody molecules to directly improve neutralization potency, which is a
major limitation to the discovery of potent and broadly reactive antibody-based interventions for viral diseases.
Current methods also cannot engineer broad antibody neutralization against related viruses, which is critical for
drug and vaccine development against diverse viral lineages. Important examples include the diverse viral
lineages of betacoronaviruses and flaviviruses, where protection against evolved and expanded viral lineages is
essential for effective clinical use.
This project will develop a new in vitro platform for rapid analysis and engineering of antibody neutralization.
We will establish methods to directly select antibodies desired antiviral properties at high throughput, including
for neutralization breadth and potency. We will apply a custom platform for natively paired antibody heavy and
light chain gene capture from human immune responses to map the neutralization capacity of antiviral antibodies
elicited by natural infection or vaccination, and to select for broad antibody protection against related viruses.
Aim 1 will establish our new assay techniques for antiviral antibody discovery and engineering against SARS-
CoV-2, which is continuously evolving after its recent emergence into human populations. This project will identify
antibody variants with high potency and breadth from the immune responses of convalescent COVID-19 patients.
We will also engineer promising antibodies for enhanced neutralization breadth and potency against diverse
SARS-CoV-2 strains.
Aim 2 will establish antiviral antibody discovery and engineering strategies against flaviviruses, using yellow
fever virus as a key model system. Antibody-dependent enhancement in flaviviruses makes potent antibody
neutralization a critical feature for any antibody-based clinical interventions. We will identify potent neutralizing
antibodies from patients vaccinated against yellow fever virus, and engineer improved neutralizing antibodies for
high potency against multiple yellow fever virus strains
This work will establish a new platform approach for potent antiviral discovery and antibody engineering. Our
long-term objectives are to develop robust and rapid antiviral antibody discovery platforms that can accelerate
progress in the development of medical interventions for viral diseases.
项目总结
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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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
- 资助金额:
$ 21.82万 - 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:
$ 21.82万 - 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:
$ 21.82万 - 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:
$ 21.82万 - 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:
$ 21.82万 - 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:
10199286 - 财政年份:2020
- 资助金额:
$ 21.82万 - 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:
$ 21.82万 - 项目类别:
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