MVA-Based H5N1 Vaccine Affords Cross-Clade Protection in Mice against Influenza AH5N1 Viruses at Low Doses and after Single Immunization 英文参考文献.docVIP

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MVA-Based H5N1 Vaccine Affords Cross-Clade Protection in Mice against Influenza AH5N1 Viruses at Low Doses and after Single Immunization 英文参考文献.doc

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MVA-Based H5N1 Vaccine Affords Cross-Clade Protection in Mice against Influenza AH5N1 Viruses at Low Doses and after Single Immunization 英文参考文献

MVA-BasedH5N1VaccineAffordsCross-CladeProtection inMiceagainstInfluenzaA/H5N1VirusesatLowDoses andafterSingleImmunization JoostH.C.M.Kreijtz1,YaseminSuezer2,GerriedeMutsert1,GeertvanAmerongen1,AstridSchwantes2, JudithM.A.vandenBrand1,RonA.M.Fouchier1,JohannesLo¨wer2,AlbertD.M.E.Osterhaus1 ,Gerd Sutter2,3,GuusF.Rimmelzwaan1* 1Department ofVirology, ErasmusMedicalCenter, Rotterdam,The Netherlands, 2Paul-Ehrlich-Institut, Langen,Germany, 3Ludwig-Maximilians-Universita¨t, Mu¨nchen, Germany Abstract Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, resultinhighmorbidityandmortality.Itisfearedthatthesevirusesbecomepandemic,thereforethedevelopmentofsafe andeffectivevaccinesisdesirable.MVA-basedH5N1vaccinesalreadyprovedtobeeffectivewhentwoimmunizationswith high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amountofvaccinepreparationsthatcanbeproducedislimited.Furthermore,protectiveimmunityisinducedideallyaftera single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccinewereassessedinmice.Tothisend,micewerevaccinatedonceortwicewithdescendingdosesofarecombinant MVAexpressingtheHAgeneofinfluenzavirusA/Vietnam/1194/04.Theprotectiveefficacywasdeterminedafterchallenge infectionwiththehomologousclade1virusandaheterologousvirusderivedfromclade2.1,A/Indonesia/5/05byassessing weightloss,virusreplicationandhistopathologicalchanges.ItwasconcludedthatMVA-basedvaccinesallowedsignificant dose-sparingandaffordcross-cladeprotection,alsoafterasingleimmunization,whicharefavorablepropertiesforanH5N1 vaccinecandidate. Citation:KreijtzJHCM,SuezerY,deMutsertG,vanAmerongenG,SchwantesA,etal.(2009)MVA-BasedH5N1VaccineAffordsCross-CladeProtectioninMice againstInfluenzaA/H5N1VirusesatLowDosesandafterSingleImmunization.PLoSONE4(11):e7790.doi:10.1371/journal.pone.0007790 Editor:JustinBrown,UniversityofGeorgia,U