Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection
RSV感染临床前模型中妊娠对疫苗诱导免疫和保护的评价
基本信息
- 批准号:10269922
- 负责人:
- 金额:$ 77.12万
- 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:2020-09-24 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAddressAdultAffectAnimal ModelAnimalsAntibody ResponseBlood group antigen fChildChildhoodClinicalClinical ResearchClinical TrialsDiseaseEnvironmentEtiologyEvaluationEvolutionExposure toFailureFemaleFormalinGoalsHumanImmuneImmune responseImmunityImmunizationInfantInfectionInfiltrationInnate Immune SystemKineticsLower Respiratory Tract InfectionLungLung diseasesLymphocyteMacacaMaternal antibodyMaternally-Acquired ImmunityMediatingMemoryMemory B-LymphocyteModelingMolecular ConformationMonoclonal AntibodiesMorbidity - disease rateMothersMucous body substanceNaturePassive ImmunityPassive Transfer of ImmunityPhenotypePopulationPre-Clinical ModelPredispositionPregnancyPreventionPrimatesProductionPublic HealthPulmonary PathologyReproducibilityRespiratory Signs and SymptomsRespiratory Syncytial Virus InfectionsRespiratory Syncytial Virus VaccinesRespiratory syncytial virusRespiratory syncytial virus RSV F proteinsRodent ModelRouteSecond Pregnancy TrimesterSerologySpecificityT-LymphocyteTestingTh2 CellsTherapeuticThird Pregnancy TrimesterVaccinatedVaccinationVaccinesVirusVirus-like particlebaseclinically relevantdesignefficacy testingexperiencehuman diseaseimmunopathologyimprovedinfant infectionmaternal vaccinationmature animalmortalityneonateneutralizing antibodyneutrophilnonhuman primatenovelnovel vaccinesoffspringperinatal periodpostnatal periodpregnantpreventprotective efficacyrecombinant virusresponseseropositivetransmission processvaccination strategyvaccine candidatevaccine developmentvaccine efficacyvaccine-induced immunity
项目摘要
RSV is the leading cause of acute lower respiratory tract infections in children, causing an estimated 33 million
new infections each year. Despite this significant global burden, there is no RSV vaccine and there are currently
limited therapeutic options for severe RSV infection. Vaccine efforts have been hindered by 1) failure of early
vaccine attempts using formalin-inactivated RSV (FI-RSV) which led to the occurrence of enhanced respiratory
disease (ERD) in some infants and 2) deficiencies of rodent models that do not to recapitulate critical aspects of
human infant RSV infection. Studies have shown that vaccination with FI-RSV and subsequent RSV challenge
skews Th2-cell mediated responses towards immunopathology, while prior exposure to live virus properly primes
the adaptive and innate immune systems without ERD. Consequently, the potential for subunit and inactivated
RSV vaccines to cause ERD remains a particular concern for RSV naïve pediatric population. In this proposal,
we offer a novel immunization strategy in a highly relevant, pre-clinical model of RSV that addresses these
barriers to vaccine development. We propose to test novel maternal immunization strategies for eliciting
protective maternal immunity and test the protective efficacy of passive transfer of neutralizing antibodies. We
hypothesize that this approach will provide protective passive immunity in infants during perinatal period of
greatest RSV susceptibility. We propose to test this approach in a non-human primate model of RSV infection
using recombinant virus-like particle (VLP) vaccines expressing F antigen in appropriate conformation. In
addition, we will use this immunization strategy to improve understanding of critical aspects of maternal
immunization including 1) the effects of pregnancy on vaccine-induced immunity 2) the kinetics of maternal
transfer of neutralizing antibodies responses and 3) the efficacy of maternal immunization and protection in a
clinically relevant infant primate model. In addition, we will define innate and adaptive immune correlates of
protection in RSV infection in adult macaques, information that will be critical to the understanding of deficiencies
in the infant lung environment. We expect these studies will have a catalytic effect on the RSV field by
establishing a pre-clinical model of infection for design and testing maternal immunization strategies as well as in
a highly relevant, pre-clinical model that most closely mimics human disease.
呼吸道合胞病毒是儿童急性下呼吸道感染的主要原因,估计造成3300万人感染
项目成果
期刊论文数量(0)
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Karen A Norris其他文献
Karen A Norris的其他文献
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{{ truncateString('Karen A Norris', 18)}}的其他基金
Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection
RSV感染临床前模型中妊娠对疫苗诱导免疫和保护的评价
- 批准号:
10119736 - 财政年份:2020
- 资助金额:
$ 77.12万 - 项目类别:
Prevention and Treatment of Pneumocystis Pneumonia
肺孢子虫肺炎的防治
- 批准号:
10605177 - 财政年份:2020
- 资助金额:
$ 77.12万 - 项目类别:
Prevention and Treatment of Pneumocystis Pneumonia
肺孢子虫肺炎的防治
- 批准号:
10382422 - 财政年份:2020
- 资助金额:
$ 77.12万 - 项目类别:
Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection
RSV感染临床前模型中妊娠对疫苗诱导免疫和保护的评价
- 批准号:
10470252 - 财政年份:2020
- 资助金额:
$ 77.12万 - 项目类别:
Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection
RSV感染临床前模型中妊娠对疫苗诱导免疫和保护的评价
- 批准号:
10685614 - 财政年份:2020
- 资助金额:
$ 77.12万 - 项目类别:
Immunopathogenesis of HIV-associated pulmonary hypertension
HIV相关肺动脉高压的免疫发病机制
- 批准号:
9370162 - 财政年份:2016
- 资助金额:
$ 77.12万 - 项目类别:
Immune dysfunction and pulmonary hypertension in primate model of HIV infection
HIV感染灵长类动物模型中的免疫功能障碍和肺动脉高压
- 批准号:
9404231 - 财政年份:2014
- 资助金额:
$ 77.12万 - 项目类别:
Serologic memory and prevention of Pneumocystis-related COPD in AIDS macaque mode
艾滋病猕猴模型肺孢子虫相关慢性阻塞性肺病的血清学记忆和预防
- 批准号:
8298380 - 财政年份:2011
- 资助金额:
$ 77.12万 - 项目类别:
T. cruzi immune evasion factors and vaccine design
克氏锥虫免疫逃避因素和疫苗设计
- 批准号:
7448591 - 财政年份:2007
- 资助金额:
$ 77.12万 - 项目类别:
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