DNA疫苗的作用机制及新型免疫策略的研究进展(1)

DNA颜凯,张倩,赵宝华(,050016)[]2006-11-22[]A[]1002-1208(2007)07-0039-04[]S852.43[]疫苗是预防和控制严重传染病的重要手段,将基因工程用于疫苗生产已经成为生物技术的热点内容之一治疗性基因工程疫苗是近些年研究的重点,并迅速从治疗传染性疾病的研究扩展到非传染性疾病的研究,如治疗性乙肝疫苗治疗性肿瘤疫苗等本文针对这一热点阐述基因工程DNA疫苗的作用机制及新型免疫策略研究的进展[]DNA疫苗;作用机制;免疫新策略:(1982-),,,,ResearchProgressontheFunctionMechanismandtheNewImmunityStrategyofDNAVaccineYANKa,iZHANGQian,ZHAOBaohua(CollegeofLifeScience,HebeiNormalUniversity,Shijiazhuang,Hebei050016;China)Abstract:Thevaccinewasanimportantmethodtopreventandcontrolseriousinfectiousdisease,soputtingthegeneticengineeringintovaccineproductionhasalreadybeenbecomingoneofthebiologicaltechnologyhotspots.Thegeneticengineeringvaccinefortherapyisthekeypointofresearchinrecentyears,andrapidlyexpandsfromthetreatmentofcommunicablediseasetothetreatmentofthenoncommunicabledisease,forexampleHBvaccineforthetreatmen,ttumorvaccineforthetreatmentandsoon.ThearticlewillelaboratethefunctionmechanismofgeneticengineeringDNAvaccineandthenewprogressofimmunitystrategy.Keywords:DNAvaccine;functionmechanism;newimmunitystrategy,,,2080,DNA,DNA,,,,[1],,DNA,DNA,[2],[3]DNA,DNA,;392007,41(7):39~41,44/,DNADNA,:DNA,;DNA,[5]DNA,,DNA:DNA,1DNA1.1抗原递呈的源头,DNA,:,,,,,(APC),APC,APC,[6];DNA,,,,APC,APC,[7],APCDNAMHCICTL;,MHCICTL,APCMHC[810]CD8+T,APC,(),,EBHIVDNAAPC,MHC!,APCVP22APC,DNA,,,MHC!,,DNA,,DNAAPC,MHC![11]1.2DNA本身的免疫特性DNA,CpGDNAB,,CpGToll9[11],,CpG,CpGCpG,DNAToll9,,,Toll9,DNA,1.3细胞因子的作用DNA,12(IL12)DNAHIVDNATh1Th2,IL2(GMCSF)[12],GMCSFHIVDNA,,LetvinHIVIL2DNA-,IL2[13],402007,41(7):39~41,44/,2DNA2.1DNA疫苗的抗原改造和疫苗载体,,[14];DNA,,,,,,,(poxvirus)(adenovirus)(alphavirus),(poliovirus)(herpesvirus)[15]2.2DNA疫苗免疫接种新策略和新型免疫佐剂,DNA+()(DNAprime+proteinboost),,,DNA,[16-18],DNA,DNA,DNA,CpG,CpGCpG,DC,1(MIP1)GMCSF3(Flt3L)[19-20],/,CD4+TIFN,,(DC),,DCDNA2.3新型材料和剂型在DNA疫苗免疫中的应用,,()[21-23],DNA,,T,,,,,,,,DNADNA,,,,,,DNA,DNA:[1]WolffJA,MaloneRW,WilliamsP,etal.DirectGeneTransferintoMouseMuscleinvivo[J].Science,1990,247:14651468.[2]ChinsangaramJ,BeardC,MasonPW,etal.AntibodyResponseinMiceInoculatedwithDNAExpressingFootandmouthDiseaseVirusCapsidProteins[J].JViro,l1998,72(5):44544457.[3]StevensonFK,OttensmeierCH,JohnsonP,etal.DNAvaccinestoattackcancer[J].PNAS,2004,101Suppl2:1464614652.[4]HuangfuT,LimLH,ChuaKY.EfficacyevaluationofDerp1DNAVaccineforAllergicAsthmainanExperimentalMouseModel[J].Vaccine,2006,24(21):45764581.[5]AmaraRR,VillingerF,AltmanJD,etal.ControlofaMucosalChallengeandPreventionofAIDSbyaMultiproteinDNA/MVAVaccine[J].Science,2001,292(5514):6974.[6]WatkinsC,HopkinsJ,HarkissG.ReporterGeneExpressioninDendriticCellsafterGeneGunAdministrationofPlasmidDNA[J].Vaccine,2005,23(33):42474256.[7]ManamS,LedwithBJ,BarnumAB,etal.PlasmidDNAVaccines:TissueDistributionandEffectsofDNASequence,AdjuvantsandDeliveryMethodonIntegrationintoHostDNA[J].Intervirology,2000,43:273281.[8]FuTM,UlmerJB,MJCaulfield,etal.PrimingofCytotoxicTLymphocytesbyDNAvaccines:RequirementforProfessionalAntigenPresentingCellsandEvidenceforAntigenTransferfromMyocytes[J].MolMed,1997,3(6):362371.(44)412007,41(7):39~41,44/,TranscriptionPCRandPCRELISA[J].ArchViro,l2001,146:8797.[8]SpackmanE,SenneDA,MyersTJ,etal.DevelopmentofaRealtimeReverseTranscriptasePCRAssayforTypeAInfluenzaVirusandtheAvianH5andH7HaemagglutininSubtyjpes[J].JClinMicrobio,l2002,40(9):32563260.[9],,,.RTPCRH5[J].,2003,(1):5963.[10],,,.RTPCRH7[J].,2005,21(7):595597.[11],,,.[J].,2006,3(1):8-12.[12],,,.H5N1[J].,2006,21(1):4346.[13],,,.H5N1A/duck/Shandong/093/2004[J].,2006,45(5):690696.[14],,,.H5N1[J].,2006,6(1):58.[15],,,.H5N1[J].,2005,27(4):282286.[16]ChenH,DengG,LiZ,etal.TheEvolutionofH5N1InfluenzaVirusesinDucksinSouthemChina[J].ProcNatlAcadSciUSA,2004,101:1045210457.[17]ChoiYK,NguyenTD,OzakiH,etal.StudiesofH5N1InfluenzaVirusInfectionofPigsbyUsingVirusesIsolatedinVietnamandThailandin2004[J].JViro,l2005,79:1082110825.[18],,.[J].,2006,31(2):122126.(41)[9]IwasakiA,TorresCA,OhashiPS,etal.TheDominantRoleofBoneMarrow-derivedCellsinCTLInductionFollowingPlasmidDNAImmunizationatDifferentSites[J].JImmuno,l1997,159:11-14.[10]DonnellyJJ,WahrenB,LiuMA.DNAVaccines:ProgressandChallenges[J].JImmuno.l2005,175(2):633-639.[11],,,.DNA[J].,2007,(1):12-14.[12]BarbaraSpies,HubertusHochrein,MartinVabulas,etal.VaccinationwithPlasmidDNAActivatesDendriticCellsviaTollLikeReceptor9(TLR9)butFunctionsinTLR9-DeficientMice[J].JournalofImmunology,2003,171:5908-5912.[13]LeeAH,SuhYS,SungYC.DNAInoculationswithHIV-1RecombinantGenomesthatExpressCytokineGenesEnhanceHIV1SpecificImmuneResponses[J].Vaccine,1999,17:473-479.[14]BarouchDH,SantraS,SchmitzJE,etal.ControlofViremiaandPreventionofClinicalAIDSinRhesusMonkeysbyCytokine-augmentedDNAVaccination[J].Science,2000,290:486-492.[15]GuevaraPatinoJA,EngelhornME,TurkMJ,etal.OptimizationofaSelfAntigenforPresentationofMultipleEpitopesinCancerImmunity[J].JClinInvest,2006,116(5):1382-1390.[16]SouzaAPD,HautL,AReyes-Sandova,letal.PintoRecombinantVirusesasVaccinesagainstViralDiseasesRecombinantVirusesasVaccines[J].BrazilianJournalofMedicalandBiologicalResearch,2005,38:509-522.[17]MooreAC,HillAV.ProgressinDNAbasedHeterologousPrimeboostImmunization