Discovery & characterization of human monoclonal antibodies targeting multiple arthritogenic alphaviruses
发现
基本信息
- 批准号:10300991
- 负责人:
- 金额:$ 5.1万
- 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:2020-07-22 至 2023-07-21
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdaptive Immune SystemAddressAedesAlphavirusAlphavirus InfectionsAnopheles GenusAntibodiesAntibody RepertoireAntibody ResponseAntibody TherapyAntiviral AgentsAntiviral TherapyArthritogenicB-LymphocytesBindingBiochemicalCaribbean regionCell SeparationCellsChikungunya virusChronicCulicidaeDevelopmentDiseaseEncephalopathiesEndemic DiseasesEpidemicEpitope MappingEpitopesEscape MutantExanthemaFeverFlow CytometryFutureHemorrhageHumanImmune responseImmune systemImmunotherapyInfectionKineticsKnowledgeMayaro virusMediatingMonoclonal AntibodiesMusMyalgiaPathogenicityPatientsPhasePolyarthralgiasPolyarthritidesPrevention therapyRNA VirusesReportingRheumatismRoss river virusSemliki forest virusSindbis VirusSiteSouth AmericaStructureTestingTherapeuticVaccine DesignVaccinesViralViruschikungunyachikungunya infectioncross reactivityemerging pathogenexperimental studyhuman monoclonal antibodieshuman pathogenin vitro testinginfectious disease treatmentinsightinterestmortalitymosquito-borneneutralizing antibodyneutralizing monoclonal antibodiesnew therapeutic targetnovelnovel therapeutic interventionresponseviral transmission
项目摘要
Project Summary
Alphaviruses are enveloped, positive sense single-stranded RNA viruses, which include several
important human pathogens. Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses
that cause human rheumatic disease and include chikungunya virus (CHIKV) and Mayaro virus (MAYV).
Symptomatic infection is characterized by fever, rash, myalgia, as well as both acute and chronic polyarthralgia
that can persist for months to years after infection. More severe manifestations of alphaviral disease –
including hemorrhage, encephalopathy and mortality – have been reported. These viruses cause endemic
disease as well as large, sporadic epidemics worldwide. Currently, there are no approved vaccines or anti-viral
therapies for the prevention or treatment of alphavirus infection; therefore, the development of new therapeutic
strategies targeting one or multiple arthritogenic alphaviruses is of substantial interest.
A number of potently neutralizing CHIKV monoclonal antibodies (mAbs) have been described, but
currently the only broadly neutralizing alphavirus mAbs that have been reported are murine. Thus, the extent to
which the human antibody response elicits broadly-neutralizing mAbs following alphavirus infection, and which
epitope(s) such mAbs may target, remains unknown. To address this question, this proposal seeks to expand
our knowledge of the neutralizing antibody response to alphaviruses by systematically investigating cross-
reactive antibodies from CHIKV-infected patients. Towards this end, we have used single B cell sorting to
isolate a large panel of MAYV-reactive mAbs from CHIKV patients in the convalescent phase. We will study
the reactivity and neutralization profiles of these mAbs against related arthitogenic alphaviruses (Aim 1). We
will then biochemically determine the requirements of neutralization (Aim 2) and elucidate the mechanism of
mAb inhibition (Aim 3). These studies will contribute to our fundamental understanding of how the adaptive
immune system combats infection by arthritogenic alphaviruses and may aid the development of novel mAb-
based treatments and vaccines.
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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Ryan J Malonis其他文献
Ryan J Malonis的其他文献
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{{ truncateString('Ryan J Malonis', 18)}}的其他基金
Discovery & characterization of human monoclonal antibodies targeting multiple arthritogenic alphaviruses
发现
- 批准号:
10445303 - 财政年份:2020
- 资助金额:
$ 5.1万 - 项目类别:
Discovery & characterization of human monoclonal antibodies targeting multiple arthritogenic alphaviruses
发现
- 批准号:
10066764 - 财政年份:2020
- 资助金额:
$ 5.1万 - 项目类别:
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