Drivers of individual variation in influenza vaccine response and protection from infection
流感疫苗反应和感染保护个体差异的驱动因素
基本信息
- 批准号:10665796
- 负责人:
- 金额:$ 145.59万
- 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:2022-07-14 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAgeAnimal ModelAntibodiesAntibody titer measurementAntigenic VariationAntigensCellsCharacteristicsComputing MethodologiesDataDevelopment PlansDimensionsDiseaseEnsureEpidemiologyEvolutionFutureGenerationsHemagglutininHeterogeneityHumanImmuneImmune responseImmunityIndividualInfectionInfluenzaInfluenza vaccinationKnowledgeLongitudinal StudiesMachine LearningMaintenanceMediationMembrane ProteinsMemoryMethodsModelingNational Institute of Allergy and Infectious DiseaseNeuraminidasePersonsPopulationPopulation HeterogeneityPublic HealthRecording of previous eventsResearchResourcesSamplingScientistSeveritiesSignal TransductionStatistical MethodsStrategic PlanningT-LymphocyteTimeTrainingUncertaintyVaccinationVaccinesVariantViralWorkcohortdesignepidemiology studyhuman modelimmunological statusimmunoregulationimprovedindividual variationinfection riskinfluenza infectioninfluenza virus vaccineinsightmultimodalityneutralizing antibodynovelnovel strategiespathogenpredicting responsepressureresponseseasonal influenzasexsingle cell analysistooluniversal influenza vaccinevaccination strategyvaccine developmentvaccine effectivenessvaccine failurevaccine responseviral fitness
项目摘要
PROJECT SUMMARY
The induction of protective immune responses through vaccination is central to the management of many
pathogens. For antigenically variable pathogens such as influenza, protective immune responses impose a major
selective pressure on viral populations and indirectly influence vaccine strain selection and vaccine
effectiveness. Our poor understanding of the generation and maintenance of protective immunity to influenza
hinders vaccine development and the accuracy of evolutionary forecasts. Antibody titers to the hemagglutinin
(HA) surface protein were established as a correlate of protection 50 years ago, and more recent evidence shows
many anti-HA antibodies directly and indirectly contribute to viral neutralization. However, HA titers remain only
moderately predictive of an individual’s risk of infection on exposure, and the contributions of other immune
responses are less well understood. Understanding the causes in addition to correlates of protection could
increase the accuracy of forecasts of viral fitness and provide reliable endpoints for vaccine development. Here,
we propose complementary approaches to identify the correlates and drivers underlying protection from infection
and heterogeneity in vaccine responses. We will integrate diverse variables, including infection and vaccination
history, baseline antigen-specific and antigen-agnostic immune states, intrinsic characteristics including age,
sex, and body mass to predict responses to influenza vaccination and extract mechanistic insight. In order to
address our specific aims, we will leverage data from existing, longitudinal studies of immune parameters
following influenza virus infections and vaccination in humans. First we will use computational and multimodal
single-cell approaches to investigate how vaccination and infection impact host immune status. Emerging
evidence, including our own data, suggests that vaccination and infection can establish new antigen-agnostic
immune set points that affect future vaccine responses. Next we propose to integrate complementary
computational approaches, spanning machine learning, causal mediation analysis, and mechanistic modeling to
predict and develop causal mechanistic insight into vaccine responsiveness and protection from severe and mild
infection. We will develop and distribute a suite of accompanying tools to make these novel approaches
accessible to bench and computational biologists. Improved prediction of immune responses, especially
protective immune responses, could lead to more effective vaccination strategies that mitigate vaccine failure in
different subpopulations and improve the public health impact of influenza vaccination. The methods and tools
that we develop can provide foundational frameworks to dissect responses to other vaccines and pathogens.
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)
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BENJAMIN JOHN COWLING其他文献
BENJAMIN JOHN COWLING的其他文献
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{{ truncateString('BENJAMIN JOHN COWLING', 18)}}的其他基金
The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study
“重复接种流感疫苗后的免疫反应动态”(DRIVE) 研究
- 批准号:
10426322 - 财政年份:2020
- 资助金额:
$ 145.59万 - 项目类别:
The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study
“重复接种流感疫苗后的免疫反应动态”(DRIVE) 研究
- 批准号:
10657605 - 财政年份:2020
- 资助金额:
$ 145.59万 - 项目类别:
The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study
“重复接种流感疫苗后的免疫反应动态”(DRIVE) 研究
- 批准号:
10035154 - 财政年份:2020
- 资助金额:
$ 145.59万 - 项目类别:
The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study
“重复接种流感疫苗后的免疫反应动态”(DRIVE) 研究
- 批准号:
10260631 - 财政年份:2020
- 资助金额:
$ 145.59万 - 项目类别:
Research on the Epidemiology, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in Southeast Asia and the Western Pacific
东南亚和西太平洋地区流感和其他呼吸道病毒的流行病学、疫苗有效性和治疗研究
- 批准号:
9761911 - 财政年份:2016
- 资助金额:
$ 145.59万 - 项目类别:
Research on the Epidemiology, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in Southeast Asia and the Western Pacific
东南亚和西太平洋地区流感和其他呼吸道病毒的流行病学、疫苗有效性和治疗研究
- 批准号:
10192599 - 财政年份:2016
- 资助金额:
$ 145.59万 - 项目类别:
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