Oral Delivery of the Sj23LHD-GST Antigen by Salmonella typhimurium Type III Secretion System Protects against Schistosoma japonicum Infection in Mice 英文参考文献.docVIP

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Oral Delivery of the Sj23LHD-GST Antigen by Salmonella typhimurium Type III Secretion System Protects against Schistosoma japonicum Infection in Mice 英文参考文献.doc

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Oral Delivery of the Sj23LHD-GST Antigen by Salmonella typhimurium Type III Secretion System Protects against Schistosoma japonicum Infection in Mice 英文参考文献

OralDeliveryoftheSj23LHD-GSTAntigenbySalmonella typhimuriumTypeIIISecretionSystemProtectsagainst SchistosomajaponicumInfectioninMice GuoChen1,YangDai2,JianxiangChen1,XiaotingWang2,BoTang1,YinchangZhu2*,ZichunHua1,3* 1TheStateKeyLaboratoryofPharmaceuticalBiotechnologyandSchoolofStomatology,AffiliatedStomatologicalHospital,NanjingUniversity,Nanjing,People’sRepublic ofChina,2KeyLaboratoryonTechnologyforParasiticDiseasesPreventionandControl,MinistryofHealthandJiangsuProvincialKeyLaboratoryonMolecularBiologyof Parasites, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, People’s Republic of China, 3Changzhou High-Tech Research Institute of Nanjing University and ChangzhouTargetPharmaLaboratoriesInc.,Changzhou,People’sRepublicofChina Abstract Background:Schistosomiasisjaponicaisazoonoticparasiticdiseaseandoralvaccinedeliverysystemwouldbebenefitfor preventionofthisdisease.Althoughattenuatedsalmonellahasbeenusedasanantigenexpressionvectorfororalvaccine development,themembrane-boundvacuolesinwhichbacteriaresidehindersthepresentationofexpressedheterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and testedtheprotectiveefficacyagainstS.japonicuminfectioninorallyimmunizedmice. Methodology/Principal Findings: Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or a-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescentmicroscopyrevealedthattheantigenwaseffectivelyexpressedanddeliveredtothecytosolofmacrophagesin vitro. Among recombinant vaccine strains, an engineeredVNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE1–104-Sj23LHD-GST) efficiently protected against S. japonicum infectioninamousemodel.ThisstrainelicitedapredominantlyIgG2a