Project 3 - USUHS
项目3-USUHS
基本信息
- 批准号:10581504
- 负责人:
- 金额:$ 63.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-20 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AnimalsAntibodiesAttenuatedAustraliaB-LymphocytesBangladeshBindingBiological AssayCell CommunicationCell fusionCell membraneCellsCellular biologyChimera organismChimeric ProteinsCommunicable DiseasesContainmentEph Family ReceptorsEphrin-A1Ephrin-B1EphrinsFar EastFerretsFutureGlycoproteinsGrowthHamstersHendra VirusHenipavirusHumanImmune responseImmunizationImmunocompetentImmunodeficient MouseImmunologic Deficiency SyndromesInfectionKineticsLivestockLuc GeneLuciferasesMammalsMediatingMedicalMembraneMembrane FusionModelingMusNipah VirusOutcomeParamyxovirusPathogenesisPathogenicityPersonsPublic HealthRNA VirusesReagentReceptor CellRecombinantsResearch Project GrantsRespiratory DiseaseSeriesSystemT-LymphocyteTechnologyTestingTexasTherapeuticTropismUniversitiesVaccinationVaccinesViralVirionVirusVirus DiseasesZoonosesbiothreatexperimental studygenetic manipulationglycoprotein Gin vivoinnovationnervous system disorderneutralizing antibodynonhuman primatenovelpathogenpathogenic virusreceptorrecombinant virusresponsereverse geneticstransmission processvaccine platformvaccine strategyvirus envelope
项目摘要
Project Summary/Abstract
The emergence and reemergence of pathogenic viruses represent continuous infectious disease threats to
public health. Among these, the paramyxoviruses, which include many important human and animal
pathogens, also include two excellent examples of emerged, zoonotic viral pathogens of importance: the
henipaviruses; Nipah virus (NiV) and Hendra virus (HeV). NiV and HeV have a uniquely broad host tropism
capable of infecting at least 18 animal species across 6 orders of mammals. NiV and HeV can also cause a
systemic and often fatal respiratory and/or neurological disease in 11 mammalian species including humans.
These henipaviruses remain significant biothreats to humans and economically important livestock in Australia
and throughout South East Asia. In addition, there are no vaccines or therapeutics approved for human use.
The henipaviruses are single-stranded, negative sense, enveloped RNA viruses and possess two membrane
anchored glycoproteins involved in virus entry, one mediates host cell receptor attachment (G glycoprotein)
and the other is a Class I fusion (F) glycoprotein which facilitates virion and host cell membrane fusion. The
viral G and F glycoproteins are the major antigenic targets of neutralizing antibodies and are the main focus of
active vaccine strategies. We have been characterizing the non-pathogenic species of henipavirus, Cedar virus
(CedPV). Using recombinant viral glycoprotein mediated cell fusion assays, we have determined that CedPV-
mediated fusion tropism is similar to NiV and HeV, however, the ephrin receptor tropism of CedPV is
remarkably broad and fusion is triggered by ephrin-B1 and -B2 as well as the glycophosphatidylinositol-
anchored A subtype ephrins-A1, -A2, and -A5. The fusion tropism activity by each of these ephrins is also
correlated with CedPV G binding, and using a recently developed reverse genetics system for preparing
recombinant CedPV (rCedPV) we have confirmed the fusion tropism findings with rCedPV infection studies.
The rCedPV platform now offers a new virological system that can be used in a variety of applications to study
henipaviruses safely under BSL-2 containment which will be broadly used by the CETR Research Projects and
Cores. But of additional importance, it is an authentic henipavirus system that is attenuated in comparison to
NiV and HeV, and can be genetically manipulated to serve as a live-attenuated universal henipavirus vaccine
platform, and one likely capable of inducting a long-lasting and balanced immune response. Using this new
system our objectives here will be to develop rCedPV chimeric viruses encoding the F and G glycoproteins of
NiV or HeV and characterize and explore their potential a novel henipavirus vaccine. Specifically, we will: 1)
Construct and rescue rCedPV-NiV/HeV viruses; 2) Characterize the chimeric viruses in cell-based infection
and tropism studies; 3) Analyze the immune responses and outcomes in both immunocompetent and
immunodeficient mice following infection with rCedPVs; 4) Test the protective abilities of rCedPVs by
vaccination in animal subjects, in response to NiV and HeV challenge.
项目总结/文摘
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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CHRISTOPHER C BRODER其他文献
CHRISTOPHER C BRODER的其他文献
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{{ truncateString('CHRISTOPHER C BRODER', 18)}}的其他基金
Advancement of Vaccines and Therapies for Henipaviruses
亨尼帕病毒疫苗和治疗的进展
- 批准号:
10581491 - 财政年份:2019
- 资助金额:
$ 63.27万 - 项目类别:
Advancement of Vaccines and Therapies for Henipaviruses
亨尼帕病毒疫苗和治疗的进展
- 批准号:
10362726 - 财政年份:2019
- 资助金额:
$ 63.27万 - 项目类别:
Advancement of Vaccines and Therapies for Henipaviruses
亨尼帕病毒疫苗和治疗的进展
- 批准号:
9897467 - 财政年份:2019
- 资助金额:
$ 63.27万 - 项目类别:
A Recombinant Cedar Virus-based Henipavirus Replication Platform for High-throughput Inhibitor Screening
基于重组雪松病毒的亨尼帕病毒复制平台,用于高通量抑制剂筛选
- 批准号:
9509144 - 财政年份:2017
- 资助金额:
$ 63.27万 - 项目类别:
Australian bat lyssavirus tropism entry and host factor dependence
澳大利亚蝙蝠狂犬病病毒的趋向性进入和宿主因子依赖性
- 批准号:
8233373 - 财政年份:2011
- 资助金额:
$ 63.27万 - 项目类别:
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