Side-by-Side Comparison of Gene-Based Smallpox Vaccine with MVA in Nonhuman Primates 英文参考文献.docVIP

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Side-by-Side Comparison of Gene-Based Smallpox Vaccine with MVA in Nonhuman Primates 英文参考文献.doc

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Side-by-Side Comparison of Gene-Based Smallpox Vaccine with MVA in Nonhuman Primates 英文参考文献

Side-by-SideComparisonofGene-BasedSmallpox VaccinewithMVAinNonhumanPrimates JosephW.Golden1,MatthewJosleyn1,EricM.Mucker2,Chien-FuHung3,PeterT.Loudon4,T.C.Wu3, JayW.Hooper1* 1Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America,2DepartmentofViralTherapeutics,VirologyDivision,UnitedStatesArmyMedicalResearchInstituteofInfectiousDiseases,FortDetrick,Maryland,UnitedStates ofAmerica,3DepartmentofPathology,JohnsHopkinsMedicalInstitutions,Baltimore,Maryland,UnitedStatesofAmerica,4Pfizer,SandwichLaboratories,Sandwich, Kent,UnitedKingdom Abstract Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serioushealthrisks,makingitsgeneralusageunacceptable.Attenuatedvaccinesarebeingdevelopedasalternatives,the mostadvancedofwhichismodified-vacciniavirusAnkara(MVA).Wepreviouslydevelopedagene-basedvaccine,termed 4pox,whichtargetsfourorthopoxvirusantigens,A33,B5,A27andL1.Thisvaccineprotectsmiceandnon-humanprimates fromlethalorthopoxvirusdisease.Here,weinvestigatedthecapacityofthemolecularadjuvantsGM-CSFandEscherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscularinjectionorthe4pox/LTvaccinedeliveredusingadisposablegenegundevice.Asapositivecontrol,oneNHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, includingthoseagainstthe4poxantigens.AfterMPXVintravenouschallenge,allcontrolNHPsdevelopedseveredisease, whiletheACAM2000vaccinatedanimalwaswellprotected.AllNHPsvaccinatedwithMVAwereprotectedfromlethality, butthreeoffivedevelopedseverediseaseandal