Human B cell responses to a live attenuated cholera vaccine
人类 B 细胞对霍乱减毒活疫苗的反应
基本信息
- 批准号:10434686
- 负责人:
- 金额:$ 39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute DiarrheaAddressAdultAffinityAfricaAgglutinationAnimal ModelAntibodiesAntibody ResponseAntigenic SpecificityAntigensAreaAttenuatedAttenuated VaccinesB-Cell ActivationB-LymphocytesBenchmarkingBiological AssayBiologyBloodCell CompartmentationCell SurvivalCellsCessation of lifeCharacteristicsChildCholeraCholera VaccineClinicCollaborationsCountryCryoelectron MicroscopyDeveloping CountriesDevelopmentDiagnosticDiarrheaDifferentiation AntigensDiseaseDoseEpidemicFDA approvedFutureGeneral HospitalsGenerationsHIVHaitiHeterogeneityHomingHumanHumoral ImmunitiesImageImmuneImmune responseImmunityImmunization ProgramsImmunogeneticsImmunoglobulin AImmunoglobulin Class SwitchingImmunoglobulin GImmunoglobulin IsotypesImmunoglobulin MImmunologicsIndividualInfectionInternationalIntestinal MucosaLeadLongevityMaintenanceMassachusettsMediatingMemoryMemory B-LymphocyteMicroscopyMonoclonal AntibodiesMucosal ImmunityMucous MembraneNegative StainingPatientsPersonsPhenotypePlasma CellsPlasmablastPopulationProcessPropertyRotavirusRouteSamplingSanitationSerotypingSpecificityTherapeuticTherapeutic UsesTravelVaccinationVaccine DesignVaccineeVaccinesVibrio choleraeVibrio cholerae infectionVirulentWaterWhole Cell VaccineWorkacute infectioncell motilitychild protectiondiarrheal diseasedimerexperienceexperimental studyhuman diseasehuman monoclonal antibodieshuman pathogeninsightlongitudinal human studymedical schoolsmigrationnovelnovel vaccinespathogenperipheral bloodpreventprotective efficacyreceptorresponsesingle cell analysisvaccine developmentvaccine-induced antibodies
项目摘要
PROJECT SUMMARY
Vibrio cholerae causes an acute diarrheal disease that is estimated to lead to 3 to 5 million cases of
cholera and causes over 100,000 deaths annually. The increasing burden of cholera, the inability to achieve
benchmarks for sanitation and safe water, and the emergence of more virulent strains of V. cholerae suggest
that more aggressive approaches to preventing cholera, including vaccination programs, are needed.
However, currently available killed whole cell vaccines generate immunity that rapidly wanes and provides only
partial protection; especially in young children. In contrast, natural infection with V. cholerae induces 90-100 %
protection against re-infection that lasts for up to 10 years in adults and children. It remains unknown why
current vaccines are markedly less effective than natural infection. Understanding mucosal immunity and
mechanisms regulating homing of immune cells to mucosal tissues in humans is of key importance, not only
for V. cholerae infection, but for many other pathogens with a mucosal route of infection.
A novel live attenuated cholera vaccine (Vaxchora) was recently approved in the US for use in
travelers. This vaccine has showed excellent protection in human challenge studies. However, little is known
about the long-term duration of protection, what determines the longevity of cholera specific memory B cells
and mucosal plasmacells, or what governs plasmacell migration to, and survival within, the intestinal mucosa.
In the current proposal, we seek to identify key differences in the early B cell responses after vaccination with
the live attenuated vaccine, that may predict long-term humoral immunity. We propose to draw upon existing
collaborations between the Emory Vaccine Center, the Emory Hope Clinic and the Massachusetts General
Hospital/Harvard Medical School (MGH/HMS) to address this question in humans. Specifically, we will study
both early and long term B cell responses in peripheral blood and in intestinal mucosae samples, using both
global and single cell approaches. These studies will provide unprecedented insight into heterogeneity of the
acute plasmablasts responses to cholera, their origin and activation process, affinity maturation and class
switching, mucosal homing potential, ability to provide long-lived immunity after infection is resolved, and the
antigenic specificity of the BCR, at a single cell level. Finally, imaging experiments will provide mechanistic
insight into the mode of action of anti-cholera antibodies. These studies will generate a large number of
monoclonal antibodies against cholera that might have both diagnostic and therapeutic uses. Findings herein
may also instruct future vaccine development for this important human pathogen.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Impact of Immunoglobulin Isotype and Epitope on the Functional Properties of Vibrio cholerae O-Specific Polysaccharide-Specific Monoclonal Antibodies.
- DOI:10.1128/mbio.03679-20
- 发表时间:2021-04-20
- 期刊:
- 影响因子:6.4
- 作者:Kauffman RC;Adekunle O;Yu H;Cho A;Nyhoff LE;Kelly M;Harris JB;Bhuiyan TR;Qadri F;Calderwood SB;Charles RC;Ryan ET;Kong J;Wrammert J
- 通讯作者:Wrammert J
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Jens Peter Wrammert其他文献
Jens Peter Wrammert的其他文献
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{{ truncateString('Jens Peter Wrammert', 18)}}的其他基金
Human B cell responses to a live attenuated cholera vaccine
人类 B 细胞对霍乱减毒活疫苗的反应
- 批准号:
10186688 - 财政年份:2018
- 资助金额:
$ 39万 - 项目类别:
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