Immune Protection Against Pulmonary Tularemia
针对肺兔热病的免疫保护
基本信息
- 批准号:8226311
- 负责人:
- 金额:$ 53.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-12-01 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AgonistAlveolar MacrophagesAnimalsAntibodiesAntigen-Presenting CellsAntigensAttentionAttenuated VaccinesBacteriaC57BL/6 MouseCellsCellular ImmunityComplexConsultationsEnzymesEventFc ReceptorFluorescence MicroscopyFrancisella tularensisFundingGenerationsImmuneImmune responseImmunityImmunobiologyImmunohistochemistryInactivated VaccinesInfectionInterleukin-12InvestigationLifeLungLymphocyte SubsetLymphoid TissueMacrophage ActivationMediatingMolecularMouse StrainsMusNatural ImmunityOrganOxidantsPathogenesisPhasePrincipal InvestigatorProcessRoleSecondary toTherapeutic UsesTimeTissuesTularemiaVaccinatedVaccinationVaccine AdjuvantVirulentadaptive immunityarmbasebiodefensecytokinedesigninfancyinsightkillingsmucosal vaccinationmutantnovelprogramsprophylacticpulmonary vaccinationrespiratoryresponsesuccesstooltraffickingvaccination strategy
项目摘要
instmctions):
Our overall objective is to develop approaches for effective vaccination against pulmonary tularemia.
During the previous funding period, we made considerable progress, including the demonstration that
significant protection in C57BL/6 mice against the highly virulent type A strain of F. tularensis {Ft), SchuS4,
can be induced by i.n. inoculation of FcR-targeted inactivated LVS {\Ft). This is the first case to our
knowledge in wliich an inactivated vaccine has provided protection against Ft SchuS4. In this
renewal application, we will further optimize conditions for mucosal vaccination, characterize the effects of
pulmonary vaccination, and define the cellular and humoral mechanisms responsible for protective immunity
against the highly virulent type A strain, SchuS4. Specifically, we will: 1) Determine the ability of i.n.
vaccination with FcR-targeted immunogens, in the absence or presence of exogenous IL-12, to enhance the
immune response to, and levels of protection against, mucosal (i.n.) challenge with Ft SchuS4. Two
separate approaches will be used to target \Ft to FcR: a) administration of preformed mAb-IFf complexes,
and b) simultaneous inoculation of uncomplexed \Ft plus anti-Ff mAb; 2) Establish the mechanisms
responsible for enhanced induction of immunity by assessing the distribution of FcR targeted \Ft to tissues
and lymphoid organs to determine if enhanced localization of '\Ft to secondary lymphoid tissues, and APC
within these tissues, occurs as a result of FcR targeting. It will also be determined if enhanced \Ft
processing and presentation results from targeting to FcR on APC; and 3) Establish the effector mechanisms
responsible for enhanced protection after i.n. vaccination with FcR-targeted bacteria. The mechanisms
responsible for protection after mucosal vaccination will be investigated by passive transfer of anti-F/
antibody or cells to naive mice with particular attention paid to examining a potential requirement for synergy
between humoral and cellular immune mechanisms for induction of effective protection. The roles of
TLR/NLRs and ROS/RNS in both inductive and effector phases will be examined by using genetically
deficient mice and specific agonists/antagonists, in consultation with the PLs of subprojects 2 and 3. The
results of subproject 1 will allow the design of new mucosal vaccination strategies for effective biodefense
against infection with virulent Ft and will provide novel insight into the pulmonary immune mechanisms that
are responsible for protection against respiratory tularemia.
RELEVANCE (See Instruct'ons):
The results of this subproject will allow the design of new mucosal vaccination strategies for effective
biodefense against infection with virulent Ft and will provide novel insight into the pulmonary immune
mechanisms that are responsible for protection against respiratory tularemia.
instmctions):
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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DENNIS W METZGER的其他文献
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{{ truncateString('DENNIS W METZGER', 18)}}的其他基金
ILC2-Mediated Protection from Acute Lung Infection
ILC2 介导的急性肺部感染保护
- 批准号:
10063550 - 财政年份:2017
- 资助金额:
$ 53.62万 - 项目类别:
Regulation of B Cell Function by Interleukin 12
白细胞介素 12 对 B 细胞功能的调节
- 批准号:
7920519 - 财政年份:2009
- 资助金额:
$ 53.62万 - 项目类别:
Effect of Influenza Infection on Alveolar Macrophage Function
流感感染对肺泡巨噬细胞功能的影响
- 批准号:
8232276 - 财政年份:2009
- 资助金额:
$ 53.62万 - 项目类别:
Effect of Influenza Infection on Alveolar Macrophage Function
流感感染对肺泡巨噬细胞功能的影响
- 批准号:
8320164 - 财政年份:2009
- 资助金额:
$ 53.62万 - 项目类别:
Effect of Influenza Infection on Alveolar Macrophage Function
流感感染对肺泡巨噬细胞功能的影响
- 批准号:
7929514 - 财政年份:2009
- 资助金额:
$ 53.62万 - 项目类别:
Effect of Influenza Infection on Alveolar Macrophage Function
流感感染对肺泡巨噬细胞功能的影响
- 批准号:
7590259 - 财政年份:2009
- 资助金额:
$ 53.62万 - 项目类别:
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