Protection of Rabbits and Immunodeficient Mice against Lethal Poxvirus Infections by Human Monoclonal Antibodies 英文参考文献.docVIP

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Protection of Rabbits and Immunodeficient Mice against Lethal Poxvirus Infections by Human Monoclonal Antibodies 英文参考文献.doc

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Protection of Rabbits and Immunodeficient Mice against Lethal Poxvirus Infections by Human Monoclonal Antibodies 英文参考文献

ProtectionofRabbitsandImmunodeficientMiceagainst LethalPoxvirusInfectionsbyHumanMonoclonal Antibodies LindsayCrickard1,TaharBabas2,SidharthSeth3,PeterSilvera2,LiliaKoriazova3,ShaneCrotty1,4* 1Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America, 2Infectious Disease Research Department,SouthernResearchInstitute,Frederick,Maryland,UnitedStatesofAmerica,3KyowaHakkoKirinCalifornia,Inc.,LaJolla,California,UnitedStatesofAmerica, 4DepartmentofMedicine,UniversityofCaliforniaSanDiegoSchoolofMedicine,LaJolla,California,UnitedStatesofAmerica Abstract Smallpox(variolavirus)isabioweaponconcern.Monkeypoxisagrowingzoonoticpoxvirusthreat.Theseproblemshave resultedinextensiveeffortstodeveloppotentialtherapeuticsthatcanpreventortreatpotentiallylethalpoxvirusinfections inhumans.Monoclonalantibodies(mAbs)againstsmallpoxareaconservativeapproachtothisproblem,asthelicensed human smallpox vaccine (vaccinia virus, VACV) primarily works on the basis of protective antibody responses against smallpox.FullyhumanmAbs(hmAbs)againstvacciniaH3(H3L)andB5(B5R),targetingboththematurevirion(MV)and extracellularenvelopedvirion(EV)forms,havebeendevelopedaspotentialtherapeuticsforuseinhumans.Post-exposure prophylaxiswasassessedinbothmurineandrabbitanimalmodels.TherapeuticefficacyofthemAbswasassessedinthree good laboratory practices (GLP) studies examining severe combined immunodeficiency mice (SCID) given a lethal VACV infection.Pre-exposurecombinationhmAbtherapyprovidedsignificantlybetterprotectionagainstdiseaseanddeaththan either single hmAb or vaccinia immune globulin (VIG). Post-exposure combination mAb therapy provided significant protectionagainstdiseaseanddeath,andappearedtofullycuretheVACVinfectionin$50%ofSCIDmice.Therapeutic efficacywasthenassessedintworabbitstudiesexaminingpost-exposurehmAbprophylaxisagainstrabbitpox(RPXV).In thefirststudy,rabbitswereinfectedwithRPVXandthenprovidedhmAbsat48hrspost-infection,or1hrand