Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination 英文参考文献.docVIP

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Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination 英文参考文献.doc

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Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination 英文参考文献

Multiple-CladeH5N1InfluenzaSplitVaccineElicitsBroad CrossProtectionagainstLethalInfluenzaVirusChallenge inMicebyIntranasalVaccination PenghuiYang1.,YueqiangDuan1.,PeiruiZhang2.,ZhiweiLi2,ChengWang3,MeiDong1,ChongTang1, LiXing1,HongjingGu1,ZhongpengZhao1,XiufanLiu4,ShaogengZhang2*,XiliangWang1* 1Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China, 2Department of Hepatobiliary, 302 Military Hospital,Beijing,China,3MedicalCollegeofSoochowUniversity,Suzhou,China,4KeyLaboratoryforAnimalInfectiousDiseasesofMinistryofAgriculture,Yangzhou University,Yangzhou,China Abstract Background:Theincreaseinrecentoutbreaksandunpredictablechangesofhighlypathogenicavianinfluenza(HPAI)H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our developmentofamultiple-cladeH5N1influenzavaccinetestedforimmunogenicityandefficacytoconfercross-protection inananimalmodel. Methodology/PrincipalFindings:Micereceivedtwodosesofinfluenzasplitvaccinewithoil-in-wateremulsionadjuvant SP01byintranasaladministrationseparatedbytwoweeks.Singlevaccines(3mgHAperdose)includedrg-A/Vietnam/1203/ 2004(Clade1),rg-A/Indonesia/05/2005(Clade2.1),andrg-A/Anhui/1/2005(Clade2.3.4).Thetrivalentvaccinecontained1 mg HAperdoseofeachsinglevaccine.Importantly,completecross-protectionwasobservedinmiceimmunizedusingtrivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenzastrain(Clade0),whereasonlythesurvivalratewasupto60%insingleA/Anhui/1/2005vaccinegroup. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protectiveimmuneresponsetoheterologousHPAIH5N1virus,thusgivingrisetoabroadlycross-reactivevaccineto potentialpreventionuseaheadofthestrain-specificpandemicinfluenzavaccineintheeventofanHPAIH5N1influenza outbreak.Also,themultiple-cladeadjuvantedvaccinecou