MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques 英文参考文献.docVIP

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MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques 英文参考文献.doc

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MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques 英文参考文献

MVA.85ABoostingofBCGandanAttenuated,phoP DeficientM.tuberculosisVaccineBothShowProtective EfficacyAgainstTuberculosisinRhesusMacaques FrankA.W.Verreck1*,RichardA.W.Vervenne1,IvanelaKondova2,KlaasW.vanKralingen3,EdmondJ. Remarque1,GercoBraskamp2,NicoleM.vanderWerff1,ArienaKersbergen1,TomH.M.Ottenhoff4, PeterJ.Heidt2,SarahC.Gilbert5,BrigitteGicquel6,AdrianV.S.Hill5,CarlosMartin7,HelenMcShane5, AlanW.Thomas1 1DepartmentofParasitology,BiomedicalPrimateResearchCentre,Rijswijk,theNetherlands,2AnimalScienceDepartment,BiomedicalPrimateResearchCentre,Rijswijk, the Netherlands, 3Department of Pulmonology, Leiden University Medical Centre, Leiden, the Netherlands, 4Department of Infectious Diseases, Leiden University MedicalCentre,Leiden,theNetherlands,5TheJennerInstitute,UniversityofOxford,Oxford,UnitedKingdom,6InstitutPasteur,Paris,France,7CentrodeInvestigacio′n Biome′dicaenReddeEnfermedadesRespiratorias(CIBERES),FacultyofMedicine,UniversityofZaragoza,Zaragoza,Spain Abstract Background:Continuoushighglobaltuberculosis(TB)mortalityratesandvariablevaccineefficacyofMycobacteriumbovis BacilleCalmette-Gue′rin(BCG)motivatethesearchforbettervaccineregimes.Relevantmodelsarerequiredtodownselect themostpromisingvaccinesenteringclinicalefficacytestingandtoidentifycorrelatesofprotection. MethodsandFindings:Here,weevaluatedimmunogenicityandprotectionagainstMycobacteriumtuberculosisinrhesus monkeyswithtwonovelstrategies:BCGboostedbymodifiedvacciniavirusAnkaraexpressingantigen85A(MVA.85A),and attenuatedM.tuberculosiswithadisruptedphoPgene(SO2)asasingle-dosevaccine.Bothstrategieswerewelltolerated, andimmunogenicasevidencedbyinductionofspecificIFNcresponses.Antigen85A-specificIFNcsecretionwasspecifically increasedbyMVA.85Aboosting.Importantly,bothMVA.85AandSO2treatmentsignificantlyreducedpathologyandchest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compa