Integrating innate and adaptive pathways in vaccine responses
将先天和适应性途径整合到疫苗反应中
基本信息
- 批准号:10265794
- 负责人:
- 金额:$ 150万
- 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:2020-06-05 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffinityAntibodiesAntigensAntiviral AgentsB-LymphocytesCell LineCellsCharacteristicsClinicalCommunicable DiseasesDengueDengue InfectionDengue VaccineDengue VirusDevelopmentDiseaseDisease susceptibilityEngineeringExhibitsFc domainFlavivirusFlavivirus InfectionsFollow-Up StudiesGene Expression ProfileGoalsHepatitis B VirusHeterogeneityHumanHuman ActivitiesIgG1ImmuneImmune responseImmune systemImmunityImmunoglobulin GImmunologic MemoryImmunologicsImmunologyIn VitroIndividualInfectionInflammatoryInfluenzaLeukocytesMediatingMedicalMemory B-LymphocyteMolecularMonoclonal AntibodiesMouse StrainsPathogenesisPathogenicityPathway interactionsPatientsPhasePolysaccharidesPopulationPredispositionProcessResearchRiceRisk FactorsRoleSeriesSeverity of illnessShapesStructureTransgenic MiceVaccinatedVaccinationVariantViralViral AntigensVirus DiseasesZIKAZIKV infectioncross reactivityepidemiologic dataglycosylationhumanized mouseimmunological statusimmunoregulationin vivoindividual responseinsightnovelnovel strategiesnovel vaccinespathogenpathogenic virusresponsesevere denguevaccination strategyvaccine response
项目摘要
ABSTRACT – Overall
Significant progress in basic immunology research over the last three decades has resulted in numerous medical
advances and dissected the general mechanisms by which the human immune system responds to foreign
antigens. However, a much more substantial understanding of the coordinated molecular mechanisms involved
in eliciting immunity will be required, as each viral pathogen poses unique challenges to the immune system and
the elicited immune responses are characterized by substantial heterogeneity that impacts disease susceptibility
and pathogenesis. Indeed, it is expected that B-cell responses against diverse viral pathogens are uniquely
evolved during infection to shape the functional activity of IgG antibodies. Studies from viral infectious diseases
have shown that antiviral IgG antibodies have the capacity to mediate a wide spectrum of opposing functions: (i)
protective functions, including neutralization, viral opsonization, and clearance of infected cells and (ii)
pathogenic activities, which enhance viral infectivity, disease susceptibility and severity; a phenomenon termed
as antibody-mediated enhancement (ADE) of disease. ADE mechanisms have been previously suggested to
account for susceptibility to dengue disease, as epidemiological data support that prior flavivirus infection is the
major risk factor for dengue disease, implicating the presence of cross-reactive, non-neutralizing IgG antibodies
to this process. Understanding the heterogeneity of IgG responses elicited upon infection or vaccination with
diverse viral antigens is therefore critical for characterizing the immunological mechanisms that drive human
immunity and determine the protective vs. pathogenic activity of IgG antibodies. Our Center will feature three
Projects directed by Drs. Ravetch (Project 1: Fc domain effector activity in dengue disease), Nussenzweig and
Rice (Project 2: Understanding B cell memory in response to diverse virus infections), and Wang (Project 3:
Immunity to dengue viruses), supported by a scientific core (Core A: Transgenic mouse core) and the
administrative core (Core B). Through a series of collaborative studies between the three Projects, our Center
aims to study human antiviral immune responses during infection and vaccination and characterize the immune
mechanisms that regulate the function of IgG antibodies in humans. More specifically, we aim to characterize
the heterogeneity of IgG responses elicited upon vaccination or infection with diverse viral pathogens, including
HBV and flaviviruses, like Zika and dengue. Additionally, we will dissect the ADE mechanisms by which IgG
antibodies mediate disease-enhancing activities and contribute to dengue disease susceptibility and
pathogenesis. These studies will provide novel insights into the mechanisms that drive protective immunity and
modulate antibody function, having a broader impact on the development of vaccination strategies against
infectious pathogens.
摘要-总体
项目成果
期刊论文数量(0)
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JEFFREY Victor RAVETCH其他文献
JEFFREY Victor RAVETCH的其他文献
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{{ truncateString('JEFFREY Victor RAVETCH', 18)}}的其他基金
Molecular mechanisms of antibody-mediated immunotherapies
抗体介导的免疫疗法的分子机制
- 批准号:
10368931 - 财政年份:2016
- 资助金额:
$ 150万 - 项目类别:
Molecular mechanisms of antibody-mediated immunotherapies
抗体介导的免疫疗法的分子机制
- 批准号:
10684073 - 财政年份:2016
- 资助金额:
$ 150万 - 项目类别:
Molecular mechanisms of antibody-mediated immunotherapies
抗体介导的免疫疗法的分子机制
- 批准号:
8940844 - 财政年份:2016
- 资助金额:
$ 150万 - 项目类别:
Molecular mechanisms of antibody-mediated immunotherapies
抗体介导的免疫疗法的分子机制
- 批准号:
10518790 - 财政年份:2016
- 资助金额:
$ 150万 - 项目类别:
Molecular mechanisms of antibody-mediated immunotherapies
抗体介导的免疫疗法的分子机制
- 批准号:
9888968 - 财政年份:2016
- 资助金额:
$ 150万 - 项目类别:
Enhanced Efficacy of MUC16 directed antibodies through modification of the Fc domain
通过修饰 Fc 结构域增强 MUC16 定向抗体的功效
- 批准号:
8933343 - 财政年份:2015
- 资助金额:
$ 150万 - 项目类别:
Integrating innate and adaptive pathways in vaccine responses
将先天和适应性途径整合到疫苗反应中
- 批准号:
10595522 - 财政年份:2014
- 资助金额:
$ 150万 - 项目类别:
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