A novel strategy for developing a SARS-CoV vaccine
A novel strategy for developing a SARS-CoV vaccine
批准号:
7904591
负责人:
Stanley Perlman
金额:
$40.33万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-12 至 2011-03-31
关键词:
ADP-Ribosylation FactorsAcademiaAnimalsAttenuatedAttenuated Live Virus VaccineBiologicalBiologyBioterrorismCellsChinaChiropteraClinicalCollaborationsCoronavirusDataDevelopmentDiseaseDisease OutbreaksE proteinEngineeringEnvironmentEpidemicFutureGene ExpressionGenerationsGenesGeneticGenetic RecombinationGenomeGoalsHamstersHumanImmuneImmunocompetentImmunologyInfectionInfectious AgentIon ChannelJointsLaboratoriesLaboratory ResearchLifeLung diseasesModelingModificationMorbidity - disease rateMusMutatePathogenesisPatientsPeptidyl-Dipeptidase APlatelet Factor 4PopulationPrivate SectorProteinsPublicationsRecombinantsRecurrenceResearchRiskSafetySevere Acute Respiratory SyndromeSystemTestingTransgenic MiceVaccine TherapyVaccinesViralVirulenceVirusVirus DiseasesVisionWild AnimalsWild Type Mouseabstractingagedbasedesignimmunogenicimmunogenicityin vivointerestmortalitynovelnovel strategiespositional cloningprematureprotein expressionprotein functionreceptorrecombinant virussuccesstissue culturetissue/cell culturetraffickingvaccine candidatevaccine developmentweapons
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Project Summary: The Severe Acute Respiratory Syndrome, caused by a novel coronavirus
(SARS-CoV), resulted in substantial morbidity and mortality in 2002-2003. With the lack of
recurrence of SARS, research efforts to develop an effective vaccine have largely halted.
However, coronaviruses similar to SARS-CoV have been identified in bats and other animal
populations in China, making recurrence of SARS a possibility. Thus, we believe that cessation
of efforts to develop a vaccine is premature. Our goal in this proposal is to develop a safe and
immunogenic live attenuated vaccine for SARS-CoV. In preliminary results, we describe what
we believe is the first candidate live attenuated vaccine. This recombinant virus lacks
expression of the envelope (E) protein, which results in an attenuated virus that causes no
disease in either hamsters or mice transgenic for expression of the SARS-CoV receptor (human
angiotensin converting enzyme, hACE2) but when used to immunize these animals, provided
partial protection against challenge with wild type SARS-CoV. The central objective of this
proposal is to develop novel live attenuated SARS-CoV vaccines that express mutated E protein
so that they are more immunogenic than E-deleted virus but remain as safe. This objective will
be achieved in the following specific aims: 1) To optimize immunogenicity of rSARS-CoV-¿E
virus by mutating rather than deleting the E protein. In this aim, we will delineate different
regions of the E protein responsible for its various biological activities. 2) To develop a mouse-
adapted rSARS-CoV with modified E protein expression, to develop rSARS-CoV-¿E
lacking expression of one or more accessory proteins and to determine the basis of
enhanced protective ability of rSARS-CoV-¿E after tissue culture passage. Mouse-
adapted SARS-CoV causes pulmonary disease. We will develop recombinant viruses that
express mutated E protein on this background. We will also optimize the vaccine by mutating
other parts of the genome. 3) To test SARS-CoV-¿E and viruses expressing mutated E as
vaccine candidates. As part of this aim, immune correlates of protection will be determined.
We will also introduce additional modifications to the virus to make recombination with
coronaviruses in the environment unlikely.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Role of eicosanoids in pathogenic human CoV infections
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批准号:9764251
-
项目类别:
-
资助金额:$54.52万
-
财政年份:2016
-
负责人:Stanley Perlman
-
依托单位:
Role of eicosanoids in pathogenic human CoV infections
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批准号:9542722
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项目类别:
-
资助金额:$54.52万
-
财政年份:2016
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负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8847630
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项目类别:
-
资助金额:$37.75万
-
财政年份:2011
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负责人:Stanley Perlman
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依托单位:
Animal Core
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批准号:8055144
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项目类别:
-
资助金额:$22.62万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8164278
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项目类别:
-
资助金额:$37.73万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8264955
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项目类别:
-
资助金额:$37.75万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8055138
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项目类别:
-
资助金额:$31.54万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8468102
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项目类别:
-
资助金额:$35.49万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Administrative Core
-
批准号:8055145
-
项目类别:
-
资助金额:$13.24万
-
财政年份:2011
-
负责人:Stanley Perlman
-
依托单位:
Role of anti-SARS-CoV T cell response in pathogenesis
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批准号:8663180
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项目类别:
-
资助金额:$37.75万
-
财政年份:2011
-
负责人:Stanley Perlman
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依托单位:
PPG: HOST VIRUS INTERACTIONS IN HCoV-SARS INFECTIONS
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批准号:7120540
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项目类别:
-
资助金额:$144.54万
-
财政年份:2004
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负责人:Stanley Perlman
-
依托单位:
PPG: SARS-CoV-host cell interactions and vaccine development
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批准号:8021280
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项目类别:
-
资助金额:$159.97万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
PPG: SARS-CoV-host cell interactions and vaccine development
-
批准号:8304203
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项目类别:
-
资助金额:$159.58万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
PPG: SARS-CoV-host cell interactions and vaccine development
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批准号:8881046
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项目类别:
-
资助金额:$159.58万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
PPG: SARS-CoV-host cell interactions and vaccine development
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批准号:9752412
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项目类别:
-
资助金额:$125.43万
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财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
Project 1
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批准号:10229390
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项目类别:
-
资助金额:$8.0万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
PPG: SARS-CoV-host cell interactions and vaccine development
-
批准号:8494515
-
项目类别:
-
资助金额:$160.57万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
Project 4
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批准号:9209901
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项目类别:
-
资助金额:$19.54万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
Development of Murine Model for SARS-CoV Pathogenesis
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批准号:6825517
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项目类别:
-
资助金额:$28.54万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
Project-004
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批准号:10229091
-
项目类别:
-
资助金额:$18.24万
-
财政年份:2004
-
负责人:Stanley Perlman
-
依托单位:
海外基金