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1、ADENOVIRUSVECTORS:ADAPTIVEIMMUNITYANDVACCINESeitherpre-existingT-cellimmunitytoAd11or,mostlikely,T-celleachcelldivision.Itisthereforedesirabletodevelopavectorthatcross-reactivitybetweenAdserotypes;ii)theuseofHDvectorscanbothintegrateintothehostgenometoac
2、hievesustainedgenedidnotpreventinductionofantiAdTcellsinnaïveanimals,andtheexpressionandbeeasilygrowntotiterssufficientforclinicaluse.incomingAdparticlesactivatedmemoryTcellresponsesininvitroWehavedevelopedahybridadenoviralvector,designatedA/RT,humanstud
3、ies;iii)wecouldnotdetectstrongantigenspecificimmunefordeliveryofanewlyisolatedhumanL1retrotransposonelement,responsesinourexperiments.Then,thesestudiessupporttheideaL1RP.Afterdeliveryviathefirst-stagehelper-dependentAdV,thethatcellularimmunity,directedto
4、theAdcapsidepitopes,isanretrotransposonelementcanmediatepermanentintegrationofimportantproblemtobesolvedforantigenspecificvaccination/transgenesinthetransducedcells.TheL1RPelementitselfexhibitsimmunotherapypurposes.oneofthehighestretrotranspositionfreque
5、nciesobservedtodate.DeliveryofanoptimizedPGKpromoter-drivenL1RPcassettein1092.Adenovirus-BasedVaccinePreventsthecontextoftheA/RThybridvectorfurtherenhancedtheoverallretrotranspositionfrequencyto15-30%ofAdV-transducedcellsasPneumoniainFerretsChallengedwit
6、htheSARSmeasuredbyreconstitutionofanintron-disruptedGFPmarkergene,Coronaviruscorrespondingtoefficienciesupto30-foldhigherthanthoseGaryP.Kobinger,1ThomasRowe,2GuangpingGao,1JoanitaM.previouslyreportedwithplasmid-baseddelivery.Hybridvector-Figueredo,1Julio
7、Sanmiguel,1PeterBell,1RobertJ.Hogan,2JamesmediatedretrotranspositionfrequencywasobservedtocorrelateM.Wilson.1withincreasingmultiplicityofinfection,andincreasedoveraperiod1GeneTherapyProgram,UniversityofPennsylvania,of6daysfollowingtransduction,thereafter
8、remainingstableatthePhiladelphia,PA;2SouthernResearchInstitute,Birmingham,AL.samelevelsfor>8weeks.RetrotranspositioneventswerealsoThehumansevereacuterespiratorysyndromecoronavirusdetectedindifferentiatedhumansomaticcells,i
