Intestinal microbiota-mediated rotavirus vaccine failure
肠道微生物介导的轮状病毒疫苗失败
基本信息
- 批准号:10586698
- 负责人:
- 金额:$ 77.25万
- 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:2022-09-19 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AntibodiesAntibody titer measurementAntigensAttenuatedAttenuated VaccinesAutomobile DrivingBacteriaBioreactorsCessation of lifeChildChildhoodDeveloping CountriesDevelopmentDiseaseDistressDoseEnterocytesEpithelialEpithelial CellsExposure toFailureFecesGoalsHealthHeterogeneityHumanImmunityIn VitroIncidenceInfantInfectionInterferonsIntestinesKnowledgeMediatingMicrobeModelingMucosal Immune ResponsesMusOralOrganoidsOutcomeOxygenPediatric cohortPhenotypePreventionPublic HealthPublishingResearchResistanceRoleRotavirusRotavirus InfectionsRotavirus VaccinesSamplingScourgeShapesSystemTestingTransplantationVaccinationVaccineeVaccinesViralViral VaccinesVirulentWorkadaptive immunitybasecohortenteric virus infectionfecal transplantationgastrointestinal epitheliumgut microbiomegut microbiotahuman microbiotamicrobialmicrobial communitymicrobiome researchmicrobiotamicrobiota transplantationmouse modelnovel strategiesoral vaccinepreventpublic health relevanceresponseunpublished worksvaccine efficacyvaccine failure
项目摘要
PROJECT SUMMARY
Infection of gut epithelia by attenuated rotavirus (RV) vaccines serves to protect millions of lives annually. It is
increasingly appreciated that gut microbiota, which shape the milieu in which rotaviruses encounter the
epithelium is a pivotal determinant of rotavirus vaccine efficacy. Indeed, RV vaccines have proven to be much
less effective in developing countries which are known to have stark differences in gut microbiota composition.
Our published work demonstrates that microbiota can both directly impact RV and, moreover, impact gut
epithelia to prevent against its entry and replication. Furthermore, our unpublished work compellingly argues for
a central role for gut microbiota composition in RV vaccine inefficacy. Specifically, we find that transplant of
microbiota from non-RV vaccine responding children confers a microbiota-dependent non-responder phenotype.
In addition, culturing infant fecal samples in bioreactor continuous culture systems yields supernatants that
differentially inhibit RV vaccine replication in vitro. Hence, the central goals of this proposal are to identify and
isolate microbiota constituents that drive RV vaccine inefficacy in humans and determine mechanisms by which
they act. Findings from this work will advance our fundamental knowledge on bacterial-viral interactions in the
gut, mechanistically enlighten how microbiota can impact replication and response to live, attenuated oral
vaccines and potentially aid in the development of novel strategies to reduce the burden of enteric viral infections.
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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Andrew T Gewirtz其他文献
Andrew T Gewirtz的其他文献
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{{ truncateString('Andrew T Gewirtz', 18)}}的其他基金
Intestinal microbiota-mediated rotavirus vaccine failure
肠道微生物介导的轮状病毒疫苗失败
- 批准号:
10707184 - 财政年份:2022
- 资助金额:
$ 77.25万 - 项目类别:
Intestinal M Cells and Secretory IgA Response to Defined Gut Microbiota
肠道 M 细胞和分泌型 IgA 对特定肠道微生物群的反应
- 批准号:
8684523 - 财政年份:2014
- 资助金额:
$ 77.25万 - 项目类别:
Intestinal M Cells and Secretory IgA Response to Defined Gut Microbiota
肠道 M 细胞和分泌型 IgA 对特定肠道微生物群的反应
- 批准号:
8793099 - 财政年份:2014
- 资助金额:
$ 77.25万 - 项目类别:
Deconstructing Inflammation and Altered Microbiota in Metabolic Syndrome
解构代谢综合征中的炎症和改变的微生物群
- 批准号:
9194750 - 财政年份:2013
- 资助金额:
$ 77.25万 - 项目类别:
Deconstructing Inflammation and Altered Microbiota in Metabolic Syndrome
解构代谢综合征中的炎症和改变的微生物群
- 批准号:
8842835 - 财政年份:2013
- 资助金额:
$ 77.25万 - 项目类别:
Deconstructing Inflammation and Altered Microbiota In Metabolic Syndrome
解构代谢综合征中的炎症和改变的微生物群
- 批准号:
8891414 - 财政年份:2013
- 资助金额:
$ 77.25万 - 项目类别:
Deconstructing Inflammation and Altered Microbiota In Metabolic Syndrome
解构代谢综合征中的炎症和改变的微生物群
- 批准号:
8609941 - 财政年份:2013
- 资助金额:
$ 77.25万 - 项目类别:
Deconstructing Inflammation and Altered Microbiota in Metabolic Syndrome
解构代谢综合征中的炎症和改变的微生物群
- 批准号:
9323386 - 财政年份:2013
- 资助金额:
$ 77.25万 - 项目类别:
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Grant-in-Aid for Scientific Research (C)














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