Combination nanovaccine-based immunization against influenza virus in the aged: immunity and protection
基于纳米疫苗的老年人流感病毒联合免疫:免疫与保护
基本信息
- 批准号:10553681
- 负责人:
- 金额:$ 71.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-16 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:AdjuvantAdultAgingAntibodiesAntibody FormationAntibody ResponseAntibody titer measurementAntigen PresentationAntigensB-Cell ActivationB-LymphocytesBiocompatible MaterialsBiology of AgingBloodCD8-Positive T-LymphocytesCell physiologyCellular ImmunityCellular Metabolic ProcessCessation of lifeCharacteristicsClinical TrialsDataDefectDendritic CellsDevelopmentDoseElderlyFormulationGoalsHealthHelper-Inducer T-LymphocyteHemagglutininHumanImmuneImmune responseImmune systemImmunityImmunizationImpairmentIn VitroIndividualInfectionInflammationInflammatoryInfluenzaInfluenza A virusInfluenza vaccinationLeadLungMeasuresMemoryMetabolicMicellesMitochondriaModelingMusNucleoproteinsOlder PopulationOutcomeOutcome MeasureOxidative PhosphorylationPhenotypePolyanhydridesPopulationPublic HealthPublishingRecombinantsResearchRespirationRiskRoleRouteSerumSpleenT cell responseT memory cellT-Cell ActivationT-LymphocyteTestingUnderserved PopulationVaccinesViral Load resultVirus Diseasesadaptive immunityage relatedagedamphiphilicityarmcell agecell motilitycopolymerdesigndraining lymph nodeflexibilityhospitalization rateshuman old age (65+)immunogenicityimprovedinfluenza infectioninfluenza virus vaccineinfluenzavirusinsightlymph nodesmetabolic profilemortalitynanoparticlenanopolymernanovaccinenonhuman primatenovelnovel strategiesperipheral bloodpreservationprimary outcomerational designrespiratoryresponsesafety studyself assemblyvaccine deliveryvaccine efficacyvaccine formulationvaccine platformvaccine responsevaccine-induced immunityyoung adult
项目摘要
PROJECT SUMMARY / ABSTRACT
Age-related defects of the immune response contribute to reduced efficacy of the influenza vaccine in older
adults. Influenza A virus (IAV) infection results in greater risk of complications and higher hospitalization rates
in older adults, with approximately 90% of deaths occurring in adults over age 65. Therefore, the development
of a safe and effective vaccine that promotes protective immunity for the aged is an urgent public health need.
The overall goal of this revised R01 application is to identify the effect of vaccine biomaterials and adjuvants on
DC metabolism, and subsequent effects on antibody and T cell memory to develop a nanovaccine to overcome
age-related immune impairments. Vaccines for older adults can be further optimized with biomaterials that
enhance multiple arms of the immune system and provide a platform to expand antigen selection, broadening
protection. Our studies will establish the contribution of specific biomaterials and adjuvants in improving B and
T cell outcomes resulting in protection by enhancing vaccine efficacy. The goals are to: 1) develop an
efficacious influenza nanovaccine for older populations; and 2) to understand the mechanisms by which
rational selection of biomaterials and co-adjuvants in vaccines can enhance immune capabilities of aged
individuals. Our two polymeric nanovaccine platforms, polyanhydride nanoparticles and pentablock copolymer
micelles, have been shown to increase antibody titers, improve cell-mediated immunity, and prolong antigen
delivery resulting in a protective immune response with reduced viral load upon delivery of recombinant
hemagglutinin and nucleoprotein in an IAV challenge model. Compelling preliminary data demonstrates that
these formulations differentially alter dendritic cell (DC) metabolic profile compared to traditional adjuvants. Aim
1 will identify how nanovaccine biomaterials and adjuvants that promote DC metabolic health augment the
immune response in aged mice. Different vaccine formulations will compare adjuvants that produce high
glycolytic responses with formulations that retain some oxidative phosphorylation and spare respiratory
capacity to optimize DC function. In the second aim, we will optimize the nanovaccine formulation(s) that
enhance B cell activation in aged mice and peripheral blood B cells from aged humans. Additionally, we will
identify mechanisms by which our nanovaccine improves T follicular helper responses and the induction of
protective immunity on an aging background. Traditional inactivated IAV vaccine will be used as a control so as
to identify the formulation providing superior protection than the current vaccine. In Aim 3, we will determine
how nanovaccine-induced metabolically-optimized DC-T cell priming contributes to T cell memory and
heterologous protection against IAV in aged mice. Measures of viral load, serum antibody, and lung T cell
responses will be evaluated in homologous and heterosubtypic IAV challenges in aged mice. The long-term
goal of this research is to define the mechanisms responsible for induction of protective immune responses in
aging populations, thus facilitating the rational design of improved vaccines for this underserved population.
项目摘要/摘要
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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Marian L Kohut其他文献
Marian L Kohut的其他文献
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{{ truncateString('Marian L Kohut', 18)}}的其他基金
Adjuvant effect of physical exercise on immune response to COVID-19 vaccination and interactions with stress
体育锻炼对 COVID-19 疫苗接种免疫反应的辅助作用以及与压力的相互作用
- 批准号:
10593597 - 财政年份:2023
- 资助金额:
$ 71.62万 - 项目类别:
Combination nanovaccine-based immunization against influenza virus in the aged: immunity and protection
基于纳米疫苗的老年人流感病毒联合免疫:免疫与保护
- 批准号:
10211470 - 财政年份:2021
- 资助金额:
$ 71.62万 - 项目类别:
Combination nanovaccine-based immunization against influenza virus in the aged: immunity and protection
基于纳米疫苗的老年人流感病毒联合免疫:免疫与保护
- 批准号:
10353425 - 财政年份:2021
- 资助金额:
$ 71.62万 - 项目类别:
Exercise-induced immunomodulation in the aged: Mechanisms
老年人运动引起的免疫调节:机制
- 批准号:
8039182 - 财政年份:2007
- 资助金额:
$ 71.62万 - 项目类别:
Exercise-induced immunomodulation in the aged: Mechanisms
老年人运动引起的免疫调节:机制
- 批准号:
7778304 - 财政年份:2007
- 资助金额:
$ 71.62万 - 项目类别:
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