Immune responses induced by a BacMam virus expressing the E2

ImmunologyLetters125(2009)145–150

ContentslistsavailableatScienceDirect

Immunology

Letters

journalhomepage:/locate

/

ImmuneresponsesinducedbyaBacMamvirusexpressingtheE2proteinofclassicalswinefevervirusinmice

MiaoLi,Yu-FeiWang,YuWang,HuiGao,NaLi,YuanSun,Bing-BingLiang,Hua-JiQiu

DivisionofSwineInfectiousDiseases,NationalKeyLaboratoryofVeterinaryBiotechnology,HarbinVeterinaryResearchInstitute,ChineseAcademyofAgriculturalSciences,427MaduanStreet,150001Harbin,Heilongjiang,China

articleinfoabstract

Non-replicatingbaculovirus-mediatedgenetransferintomammaliancellshasbeendevelopedasavac-cinestrategyagainstanumberofdiseasesinseveralanimalmodels.Inthepresentstudy,theBacMamvector,abaculoviruspseudotypedwiththeglycoproteinfromvesicularstomatitisvirus,wasusedasarecombinantvectortoexpressclassicalswinefevervirus(CSFV)E2proteinunderthecontroloftheimmediateearly1(ie1)promoterfromshrimpwhitespotsyndromevirus.TheE2genewasef cientlyexpressedinbothinsectandmammaliancells.Intramuscularinjectionofmicewiththerecombinantbaculovirusresultedintheproductionofhigh-titersofCSFV-speci cneutralizingantibodies.Speci clymphoproliferativeresponsestoCSFVstimulationweredetectedinthesplenocytesoftheimmunizedmiceasdemonstratedbyCFSEstainingassayandWST-8assay.ThisstudydemonstratesthattheBacMamvirusvectorcanef cientlyexpresstheE2proteinandeffectivelyinduceimmuneresponsesagainstCSFV.Thisisa rststepinthedemonstrationthatthepseudotypedbaculovirus-deliveredCSFVE2genecanbeapotentialnon-replicatingvaccineagainstCSFVinfections.

©2009ElsevierB.V.Allrightsreserved.

Articlehistory:

Received23January2009

Receivedinrevisedform28June2009Accepted1July2009

Availableonline7July2009Keywords:

ClassicalswinefevervirusE2gene

BacMamvirus

RecombinantbaculovirusImmunogenicity

1.Introduction

Thebaculovirusexpressionsystemhasbeenextensivelyusedasvectorsforabundantexpressionofalargevarietyofforeignproteinsininsectcells.Recently,recombinantbaculovirusvectorscontainingmammaliancell-activepromoterelements(alsoknownasBacMamviruses)havebeenusedsuccessfullyforgenedeliv-eryintomammaliancelllineswithoutapparentviralreplication[1].RecentstudieshavedemonstratedthatBacMamvirusescanbeusednotonlyforef cientgenetransductionintomammaliancellsinvitro[2,3]butalsoforgenetransductioninvivo[4,5].ThemajoradvantageoftheBacMamvirusisthatitshowsef cientgenetransductionintoawidevarietyofcelllinesbydirectinfection.Numerouseffortshavebeenmadetoharnessthebaculovirusasavectorforgenetherapyandvaccinedevelopment.Theuseofbac-ulovirusasavectorforvaccinationwasinitiallydescribedbyAokietal.[6],whodemonstratedthatintramuscularinjectionofmicewitharecombinantbaculovirusexpressingthepseudorabiesvirusgBproteincouldelicitedameasurablehumoralresponse.Further-more,severalgroupshavedemonstratedthatdirectvaccinationwithrecombinantbaculovirusbyintramuscular,intraperitonealorintranasalinoculationcaninducetheproductionofhumoral

Correspondingauthor.Tel.:+8645185935041;fax:+8645185935041.E-mailaddress:huajiqiu@(H.-J.Qiu).0165-2478/$–seefrontmatter©2009ElsevierB.V.Allrightsreserved.doi:10.1016/j.imlet.2009.07.001

andcell-mediatedimmunityagainstvariousantigens[7–9].Morerecently,Wangetal.[10]reportedthatanimmuneresponsetotheGP5andMproteinsofporcinereproductiveandrespiratorysyn-dromeviruswaseliciteduponvaccinationwithabaculovirusvectorexpressingthevirusstructuralcomponent.

Classicalswinefever(CSF),whichiscausedbyclassicalswinefevervirus(CSFV),isafatalswinediseaseandoneofdiseaseslistedbytheWorldOrganizationforAnimalHealth(OIE).Thediseaseisendemicorepidemicinmanycountriesandcausesgreateconomiclosstotheswineindustryworldwide.TheCSFVgenomecontainsasingle,largeopenreadingframe(ORF)encodingapolyproteinthat,uponproteolyticprocessing,givesrisetofourstructuralpro-teinsandeightnon-structuralproteins[11].TheE2proteinisanenvelopeglycoprotein,whichisresponsibleforelicitingneutraliz-ingantibodiesininfectedanimalsandthusprotectingpigsagainstvirulentchallenge.

Atpresent,themostfrequentlyusedvaccineistheChineselapinizedattenuatedvaccine,i.e.C-strain,whichcaninducecom-pleteprotectionagainstCSF.However,amajordisadvantageofthisvaccineisthattheantibodiesinducedbythevaccinecannotbedis-tinguishedfromthoseinducedbywild-typeCSFVinfections.ItisimportanttodevelopnovelCSFVvaccinescapableofinducingrapidprotectioncombinedwiththeabilitytodifferentiateinfectedfromvaccinatedanimals.

OurpreviousstudiesdemonstratedthattheBacMamviruswithanEGFPreportergeneunderthecontroloftheshrimpwhitespotsyndromevirus(WSSV)immediateearly1(ie1)promoterexhib-