Protection against Enterovirus 71 with Neutralizing Epitope Incorporation within Adenovirus Type 3 Hexon 英文参考文献.docVIP

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Protection against Enterovirus 71 with Neutralizing Epitope Incorporation within Adenovirus Type 3 Hexon 英文参考文献.doc

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Protection against Enterovirus 71 with Neutralizing Epitope Incorporation within Adenovirus Type 3 Hexon 英文参考文献

ProtectionagainstEnterovirus71withNeutralizing EpitopeIncorporationwithinAdenovirusType3Hexon XinguiTian1,XiaoboSu2,XiaoLi1,HaitaoLi1¤,TingLi1,ZhichaoZhou1,TianhuaZhong1,RongZhou1* 1StateKeyLabofRespiratoryDisease,TheFirstAffiliatedHospitalofGuangzhouMedicalCollege,Guangzhou,Guangdong,China,2DepartmentofMedicalGeneticsand CellBiology,SchoolofBasicScience,GuangzhouMedicalCollege,Guangzhou,Guangdong,China Abstract Enterovirus 71 (EV71) is responsible for hand, foot and mouth disease with high mortality among children. Various neutralizingBcellepitopesofEV71havebeenidentifiedaspotentialvaccinecandidates.Capsid-incorporationofantigens intoadenovirus(Ad)hasbeendevelopedforanovelvaccineapproach.WeconstructedAd3-basedEV71vaccinevectorsby incorporatinganeutralizingepitopeSP70containing15aminoacidsderivedfromcapsidproteinVP1ofEV71withinthe different surface-exposed domains of the capsid protein hexon of Ad3EGFP, a recombinant adenovirus type 3 (Ad3) expressing enhanced green fluorescence protein. Thermostability and growth kinetic assays suggested that the SP70 epitopeincorporation intohypervariable region(HVR1,HVR2,orHVR7) ofthehexon didnotaffectAdfitness.TheSP70 epitopeswerethoughttobeexposedonallhexon-modifiedintactvirionsurfaces.RepeatedadministrationofBALB/cmice with the modified Ads resulted in boosting of the anti-SP70 humoral immune response. Importantly, the modified Ads immunization of mother mice conferred protection in vivo to neonatal mice against the lethal EV71 challenge, and the modified Ads-immunized mice serum also conferred passive protection against the lethal challenge in newborn mice. Compared with the recombinant GST-fused SP70 protein immunization, immunization with the Ads containing SP70 in HVR1orHVR2elicitedhigherSP70-specificIgGtiters,higherneutralizationtiters,andconferredmoreeffectiveprotectionto neonatalmice.Thus,thisstudyprovidesvaluableinformationforhexon-modifiedAd3vectordevelopmentasapromising EV71vaccinecandidateandasanepitope-deliver