Mechanisms of antibody-mediated control of repeated hepatitis C virus infection in humans
抗体介导控制人类丙型肝炎病毒重复感染的机制
基本信息
- 批准号:10205733
- 负责人:
- 金额:$ 51.63万
- 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:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffinityAnimal ModelAntibodiesAntibody ResponseAntibody titer measurementAntigenic VariationAntigensAntiviral AgentsAutologousAutomobile DrivingB cell repertoireB-Cell ActivationB-LymphocytesB-cell receptor repertoire sequencingBindingBinding SitesBiological AssayBlocking AntibodiesCD4 Positive T LymphocytesCD81 geneCellsChronicClone CellsCollaborationsComplexDevelopmentDisease OutcomeEpitopesEvolutionExposure toFlow CytometryFunctional disorderHIV-1Hepatitis CHepatitis C AntibodiesHepatitis C VaccineHepatitis C virusHumanImmuneImmune responseImmunoglobulin Somatic HypermutationIn VitroIndividualInfectionInfusion proceduresLinkMeasuresMediatingModelingMonoclonal AntibodiesParticipantPhenotypePlasmaPlayProteinsResistanceRoleSiteStimulusStructureStudy SubjectT cell responseT-LymphocyteTestingTimeVaccinesVariantViralViremiaVirusVirus DiseasesWorkadaptive immunitybasechronic infectionenv Gene Productshigh dimensionalityhuman subjectin vivoneutralizing antibodynovelpressureresponsesingle-cell RNA sequencingvaccine candidatevaccine developmentvaccine response
项目摘要
Project Summary
Broadly neutralizing antibodies (bNAbs) block infection by diverse HCV strains in vitro, and infusion of bNAbs
is protective against HCV infection in animal models. In contrast to some other chronic viral infections like HIV-
1 where bNAbs do not appear to influence disease outcome, early development of high plasma bNAb titers is
associated with spontaneous clearance of primary HCV infection in humans. Although it is clear that bNAbs
can play a critical role in clearance of primary HCV infection, detailed analysis of antibody titers, epitopes
targeted, and B cell phenotypes associated with clearance of infection are still lacking. Individuals who clear
multiple reinfections may be the ideal study subjects to further define protective antibody responses. Of those
who clear their first infection, 80% clear subsequent reinfections with a rapid rise in neutralizing antibody (NAb)
titers, shorter duration of infection, and lower peak viremia, demonstrating protective adaptive immunity that
can serve as a model for a desired vaccine response. It is not known which parameters of the B cell response
are most critical for repeated clearance of infection, or what antigenic stimuli are necessary for induction of
these responses.
In Aim 1 of this proposal, we will define plasma anti-HCV antibody binding and neutralizing activity associated
with repeated clearance of reinfection. In Aim 2, we will determine the mechanistic basis for changes in
neutralizing activity by characterizing the dynamic interplay between the circulating B cell repertoire and HCV
sequence changes during reinfection. In Aim 3, we will define phenotypes of HCV-specific B cells associated
with repeated clearance of reinfection.
Because reinfections are generally cleared very efficiently, these immune responses can serve as a model for
responses that should be induced by a vaccine. By characterizing plasma antibody responses, B cell
repertoires, viral antigenic variation, and B cell phenotypes in human subjects with repeated spontaneous
clearance of infection, we will inform HCV vaccine development.
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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Justin Richard Bailey其他文献
Justin Richard Bailey的其他文献
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{{ truncateString('Justin Richard Bailey', 18)}}的其他基金
Molecular and structural characterization of broadly neutralizing anti-HCV antibodies
广泛中和抗 HCV 抗体的分子和结构表征
- 批准号:
10657917 - 财政年份:2023
- 资助金额:
$ 51.63万 - 项目类别:
The role of neutralizing antibodies in natural and treatment-induced control of hepatitis B with and without HIV-1 co-infection
中和抗体在自然控制和治疗诱导控制有或没有 HIV-1 合并感染的乙型肝炎中的作用
- 批准号:
10618760 - 财政年份:2023
- 资助金额:
$ 51.63万 - 项目类别:
Neutralizing antibody responses during natural control of acute hepatitis B with and without HIV-1 coinfection
在有或没有 HIV-1 合并感染的急性乙型肝炎自然控制过程中中和抗体反应
- 批准号:
10402216 - 财政年份:2022
- 资助金额:
$ 51.63万 - 项目类别:
Neutralizing antibody responses during natural control of acute hepatitis B with and without HIV-1 coinfection
在有或没有 HIV-1 合并感染的急性乙型肝炎自然控制过程中中和抗体反应
- 批准号:
10674691 - 财政年份:2022
- 资助金额:
$ 51.63万 - 项目类别:
Development of standardized immunoassays and virus panels for HCV vaccine research
开发用于 HCV 疫苗研究的标准化免疫测定和病毒组
- 批准号:
10172194 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Mechanisms of antibody-mediated control of repeated hepatitis C virus infection in humans
抗体介导控制人类丙型肝炎病毒重复感染的机制
- 批准号:
10614981 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Mechanisms of antibody-mediated control of repeated hepatitis C virus infection in humans
抗体介导控制人类丙型肝炎病毒重复感染的机制
- 批准号:
10398151 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Development of standardized immunoassays and virus panels for HCV vaccine research
开发用于 HCV 疫苗研究的标准化免疫测定和病毒组
- 批准号:
10456321 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Development of standardized immunoassays and virus panels for HCV vaccine research
开发用于 HCV 疫苗研究的标准化免疫测定和病毒组
- 批准号:
10655523 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Molecular and structural characterization of broadly neutralizing anti-HCV antibodies
广泛中和抗 HCV 抗体的分子和结构表征
- 批准号:
9478874 - 财政年份:2017
- 资助金额:
$ 51.63万 - 项目类别:
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