Protective Antiviral Immunity Conferred by a Nonintegrative Lentiviral Vector-Based Vaccine 英文参考文献.docVIP

ProtectiveAntiviralImmunityConferredbya NonintegrativeLentiviralVector-BasedVaccine Fre′de′ricCoutant1,Marie-PascaleFrenkiel2,PhilippeDespres2,PierreCharneau1* 1LaboratoiredeVirologieMole′culaireetVectorologie,InstitutPasteur,Paris,France,2Unite′ desInteractionsMole′culairesFlavivirus-Ho?tes,InstitutPasteur,Paris,France Abstract Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogensbecauseoftheirabilitytoinitiatepotentanddurablespecificimmuneresponses.Strategiesthatalleviatesafety concernswillfacilitatetheclinicaldevelopmentsinvolvinglentiviralvectors.Inthisrespect,thedevelopmentofintegration deficientlentiviralvectorscircumventsthesafetyconcernsrelativetoinsertionalmutagenesisandmightpavethewayfor clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non- dividingdendriticcell(DC).Inthisstudy,wedemonstratedthatasingleadministrationofnonintegrativevectorsencodinga secretedformoftheenvelopeofavirulentstrainofWestNileVirus(WNV)inducesarobustBcellresponse.Remarkably, nonintegrativelentiviralvectorsfullyprotectedmicefromachallengewithalethaldoseofWNVandasingleimmunization wassufficienttoinduceearlyandlong-lastingprotectiveimmunity.Thus,nonintegrativelentiviralvectorsmightrepresenta safeandefficaciousvaccinationplatformforthedevelopmentofprophylacticvaccinesagainstinfectiousagents. Citation:CoutantF,FrenkielM-P,DespresP,CharneauP(2008)ProtectiveAntiviralImmunityConferredbyaNonintegrativeLentiviralVector-BasedVaccine.PLoS ONE3(12):e3973.doi:10.1371/journal.pone.0003973 Editor:TorbjornRamqvist,KarolinskaInstitutet,Sweden ReceivedAugust7,2008;AcceptedNovember19,2008;PublishedDecember19,2008 Copyright: ? 2008 Coutant et al. This is an open-access article distributed under the terms of the Creative Commons Attribution L