Bioactive Components in Breast Milk Impact Rotavirus Vaccine Response
母乳中的生物活性成分影响轮状病毒疫苗反应
基本信息
- 批准号:10354154
- 负责人:
- 金额:$ 19.15万
- 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:2022-02-18 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:5 year oldAcuteAfrica South of the SaharaAgeAttenuatedBinding ProteinsBiological AssayBlood Group AntigensBreast FeedingCapsid ProteinsCessation of lifeChildChild HealthChildhoodCold ChainsCommunicable DiseasesComplexConflict (Psychology)Controlled Clinical TrialsCountryDataData AnalysesDevelopmentEffectivenessEnteralEvidence based interventionFoundationsFunctional disorderFutureGastroenteritisGenerationsGeneticGoalsHerd ImmunityHuman MilkHygieneImmune responseImmunization ProgramsImmunoglobulin AIn VitroIncomeIndiaIndividualInfantInterventionIntervention StudiesLaboratory StudyMaintenanceMalnutritionMaternal antibodyMicrobeMorbidity - disease rateMothersMucosal ImmunityNeonatalOligosaccharidesOralOutcomePolysaccharidesPopulationProbioticsPublic HealthRoleRotavirusRotavirus InfectionsRotavirus VaccinesSamplingSanitationSoutheastern AsiaTemperatureTestingVaccine Clinical TrialVaccinesValidationWorkbasebreast milk microbiomeburden of illnesscohortcommensal bacteriacompare effectivenesscostcost effectivediarrheal diseaseenteric infectionevidence basegastrointestinalgastrointestinal infectiongut microbiomeimmunogenicityimprovedinfant gut microbiomeinsightlow and middle-income countriesmicrobialmicrobiomemicrobiome compositionmilk microbiomemortalityoral vaccinepathogenprebioticsrecruitresponders and non-responderssuccesssugarvaccine efficacyvaccine response
项目摘要
PROJECT SUMMARY
Despite the introduction of live attenuated oral rotavirus vaccines (ORVs) in over 100 countries, rotavirus (RV)
remains the leading cause of acute gastroenteritis in children under the age of 5. This is because ORV efficacy
in most low- and middle-income countries (LMICs) is only about 50% compared to nearly 90% efficacy in high-
income countries. These differences are not specific to one vaccine or one country; all WHO pre-qualified ORVs
show sub-optimal efficacy in LMICs. This is also not an issue of vaccine coverage or cold chain requirements
since poor efficacy was observed even within well controlled clinical trials. ORVs have several advantages
including low costs, ease of administration, ability to generate mucosal immunity and generation of herd immunity
through vaccine shedding. Efforts to improve ORV efficacy will therefore have substantial public health impact.
Our long-term goal is to develop evidence-based interventions to improve ORV response in settings with
high disease burden. Critical steps include understanding what factors distinguish vaccine responders from non-
responders within a population and identifying modifiable factors that will enable the development of targeted
interventions. With this objective, we focus on bioactive components in breastmilk. We hypothesize: (i) Bioactive
components in breast milk are key modulators of ORV response, and (ii) A combination of maternal factors and
infant factors will be more predictive of differences in vaccine response than any individual factor. The rationale
for this hypothesis is our recent work demonstrating a role for interactions between human milk oligosaccharides
(HMOs), the milk microbiome and infant gut microbiome in promoting neonatal RV infections. New data also
indicate that consideration of maternal and infant genetic differences in glycan expression provides a more
comprehensive picture of gastrointestinal infections and vaccine responses than previously recognized. In strong
preliminary data, we show that HMOs and the milk microbiome can directly modulate the in vitro infectivity of
Rotavac, an asymptomatic neonatal rotavirus strain-derived ORV used in India’s national immunization program.
Like other ORVs in LMICs, Rotavac also has sub-optimal efficacy but is remarkably cost effective and can
substantially reduce RV-associated burden if vaccine efficacy is improved. HMOs, commensal bacteria and
microbial products have the potential to be developed as prebiotics and probiotics and thus are attractive
candidates for future development as interventions.
In two specific aims we ask: 1) Is the composition and functional activity of breast milk bioactive components
different between vaccine responders and non-responders? 2) Does the combination of maternal factors and
covarying infant factors better predict ORV response than any factor individually?
Our short-term goal is to gain critical insight into the role of breast milk bioactive components in ORV response.
Our long-term goal is to test identified candidates in future mechanistic and functional studies aimed at
developing probiotics and prebiotics that can be co-administered with ORVs.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sasirekha Ramani其他文献
Sasirekha Ramani的其他文献
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{{ truncateString('Sasirekha Ramani', 18)}}的其他基金
Bioactive Components in Breast Milk Impact Rotavirus Vaccine Response
母乳中的生物活性成分影响轮状病毒疫苗反应
- 批准号:
10576980 - 财政年份:2022
- 资助金额:
$ 19.15万 - 项目类别:
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