A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models 英文参考文献.docVIP

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A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models 英文参考文献.doc

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A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models 英文参考文献

AWholeVirusPandemicInfluenzaH1N1VaccineIs HighlyImmunogenicandProtectiveinActive ImmunizationandPassiveProtectionMouseModels OtfriedKistner,BrianA.Crowe,WalterWodal,AstridKerschbaum,HelgaSavidis-Dacho,Nicolas Sabarth,FalkoG.Falkner,InesMayerhofer,WolfgangMundt,ManfredReiter,LeopoldGrillberger, ChristaTauer,MichaelGraninger,AloisSachslehner,MichaelSchwendinger,PeterBru¨hl,ThomasR. Kreil,HartmutJ.Ehrlich,P.NoelBarrett* GlobalResearchandDevelopment,BaxterBioScience,Vienna,Austria Abstract Therecentemergenceandrapidspreadofanovelswine-derivedH1N1influenzavirushasresultedinthefirstinfluenza pandemicofthiscentury.Monovalentvaccineshaveundergonepreclinicalandclinicaldevelopmentpriortoinitiationof mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunizationofmice,whichindicatethatawholevirus,nonadjuvantedvaccineisimmunogenicatlowdosesandprotects againstliveviruschallenge.TheimmunogenicityinthismodelwascomparabletothatofawholevirusH5N1vaccine,which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemicvaccineinprotectingagainstliveviruschallengewasalsoseentobeequivalenttothatoftheH5N1vaccine.The protectiveefficacyoftheH1N1vaccinewasalsoconfirmedusingaseverecombinedimmunodeficient(SCID)mousemodel. ItwasdemonstratedthatmouseandguineapigimmuneseraelicitedfollowingactiveH1N1vaccinationresultedin100% protectionofSCIDmicefollowingpassivetransferofimmuneseraandlethalchallenge.Theimmuneresponsestoawhole viruspandemicH1N1andasplitseasonalH1N1vaccinewerealsocomparedinthisstudy.Itwasdemonstratedthatthe wholevirusvaccineinducedabalancedTh-1andTh-2responseinmice,whereasthesplitvaccineinducedmainlyaTh-2 responseandonlyminimallevelsofTh-1responses.Thesedatasupportedtheinitiationofclinicalstudieswiththesame low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a wholevirusH5N1vaccine. Citati