人乳头瘤病毒防治疫苗的应用研究进展-刘静-(1)

:1003-6946(2010)01-017-04人乳头瘤病毒防治疫苗的应用研究进展刘　静1　,糜若然2　(1.,300052;2.,300052)【】　预防性疫苗以人乳头瘤病毒(HPV)晚期结构蛋白L1、L2诱导引发特异性抗体来抵抗HPV感染,治疗性疫苗通过早期HPV基因编码蛋白的抗原表位来产生免疫反应。研发预防性HPV疫苗是防治宫颈癌的一个重要里程碑,其能对抗特定的致癌性HPV型的最初感染,治疗性疫苗对治疗HPV感染相关的宫颈恶性病变带来了契机,但其安全性及远期疗效仍需深入研究。作者探讨了有关HPV感染与宫颈癌流行病学关系、HPV感染与机体免疫反应等妇科肿瘤学的基本问题,着重对HPV防治性疫苗作用机制、生物学特性及其应用现状等作一阐述。【】　人乳头瘤病毒;感染;免疫;疫苗:R373　　　　:B　　,47,30,。,99%(HPV)。HPV。HPVHPV,HPV、HPV。1　HPV　　HPV。HPV40,()HPV、HPVHPV,HPVHPVHPV16、18、45、31、33、58;,HPV16、18、31、4575%,HPV1651.0%。PCR99.17%HPV。HPV16、18、31、33,HPV16、18;,HPV16;HPV18;HPV[1]。HPV16、18,。HPV(CIN)。,HPV-DNACINⅢHPV-DNA。HPV,。,,。,,,,,,,、。,、、、,,,。PPCM,,。、,,、,。,、,,,。,,、、,。(:2009-10-13;:2009-11-05)·17·20101261　JournalofPracticalObstetricsandGynecology2010Jan.Vol.26,No.1E6、E7E6、E7,[2]。2　HPV　　HPV。HPV,HPV,。,HPVE6E7,,[3]。Kang[4]HPV16E6、E7(immuneinterfer-on,IFN)18(IL-18)。,E6E7。E6E7。　　IgA、IgG,,,,,[5]。,E-,E6E-,L1,,。HPV,HPV。HPV16IgAIgG[6]。HPV16E6E7IL-18IFN-r。NK、T(LC)。HPV,NK、TLC,。3　HPV　　,,,HPV-DNA,,、。HPV,HPV,、[7]。,,。HPV。　　HPV,HPVL1、L2,L1L2,(viruslikeparticles,VLP),VLP,,[8]。,,,,,HPVL1、L2HPV。3.1　HPV　HPV16L1VLP,HPV16L1,,,,。HPV16L1,VLP,,。3.2　HPV　FDAGarda-sil、CervarixVLP,L1,1618,HPV161870%。BayasGardasilCervarixHPVCIN,1、2,,3、4,HPVCIN,100%,Gardasil、。HPV(HPV4531)。Bayas[9]8～14,,。Govan[10]Gardasil5。HPV16/18ASO42、36.4。Schwarz[11],,B,HPV16/18ASO4。Harper[12]25.5,·18·20101261　JournalofPracticalObstetricsandGynecology2010Jan.Vol.26,No.115～253,2、3HPV16/18ASO4HPV16/18100%。HPV,HPVHPV,HPV。4　HPV　　,。HPV(E6、E7),(Ll、L2)。4.1　　HPVE6、E7,T(CTL)。HPV16E7HPV16。,,HLA。,ⅠⅡ。4.2　DNA　,HPV,E6E7,,,E6E7HPV,THPVHPV。,HPVE6E7T,DNA[13,14]。Huang[15]DNA,DNARNA(shRNA)(Knock-out),(luciferasegene)。HuangshRNADNA,E7DNAshRNAFaslDNAE7CD8(+)TE7。,shRNADNA,DNA。Tseng5(deathreceptor5,DR5)HPVE7DNA,DNAE7CD8(+)T,Tseng[16]MD5-1TC-1E7T,。DNA,。4.3　　DNAHPVDNADNA,E6、E7,T,HPV。,。、。Swell[17]HPV16E7,、CD8(+)T。。4.4　　(dendriticcells,DC)(professionalantigen-presentingcells,PAPC),,MHC-Ⅰ。,。DCHPVDC、HPVDNADCDC,,T。Hung[18]DCHPVDNA,HPV16E7MHCIⅡ。5　　　,Brotherton[19]BrightonHPV,12,8,BrothertonHPV,,。Studdif-ord[20]126HPV(3),2。HPV。,。,:①;②;③;④。·19·20101261　JournalofPracticalObstetricsandGynecology2010Jan.Vol.26,No.1,HPV,HPV,HPV,,,。、,HPV。[1]　TaySK,NganHY,ChuTY,etal.Epidemiologyofhumanpapilloma-virusinfectionandcervicalcancerandfutureperspectivesinHongKong,SingaporeandTaiwan[J].Vaccine,2008,26(12):60-70.[2]　GiulianoAR,Tortolero-LunaG,FerrerE,etal.Epidemiologyofhu-manpapillomavirusinfectioninmen,cancersotherthancervicalandbenignconditions[J].Vaccine,2008,26(10):17-28.[3]　KocjanBJ,SemeK,PoljakM.DetectionanddifferentiationofhumanpapillomavirusgenotypesHPV-6andHPV-11byFRET-basedreal-timePCR[J].JVirolMethods,2008,153(2):245-249.[4]　KangYH,LeeKA,RyuCJ,etal.MitomycincinducesapoptosisviaFas/FasLdependantpathwayandsuppressionofIL-18incervicalcar-cinomacells[J].CancerLett,2006,237(1):33-34.[5]　ReuschenbachM,WaterboerT,WallinKL,etal.CharacterizationofhumoralimmuneresponsesagainstP16,P53,HPV16E6andHPV16E7inpatientswithPHV-associatedcancers[J].IntJCancer,2008,123(11):2626-2631.[6]　RosenthalSL,RuppR,ZimetGD,etal.UptakeofHPVvaccine:de-mographics,sexualhistoryandvalues,parentingstyle,andvaccineatti-tudes[J].JAdolescHealth,2008,43(3):239-245.[7]　MyersE,HuhWk,WrightJD,etal.ThecurrentandfutureroleofscreeningintheeraofHPVvaccination[J].GynecolOncol,2008,109(2):31-39.[8]　KandaT,KondoK.DevelopmentofanHPVvaccineforabroadspec-trumofhigh-risktypes[J].HumVaccin,2008,5(1):38-42.[9]　BayasJM,CostasL,MunozA.Cervicalcancervaccinationindica-　　tions,efficacy,andsideeffects[J].GynecolOncol,2008,110(3):11-14.[10]GovanVA.Anovelvaccineforcervicalcancer:quadrivalenthumanpapillomavirus(types6,11,16and18)recombinantvaccine(garda-sil)[J].TherClinRiskManag,2008,4(1):65-70.[11]SchwarzTF,LeoO.ImmuneresponsetohumanpapillomavirusafterprophylacticvaccinationwithASO4-adjuvantedHPV-16/18vaccine;improvinguponnature[J].GynecolOncol,2008,110(1):1-10.[12]HarperDM.Impactofvaccinationwithcervarixtrademarkonsubse-quentHPV-16/18infectionandcervicaldiseaseinwomen15-25yearsofage[J].BJOG,2008,115(8):938-946.[13]PoolmanEM,ElbashaEH,GalvaniAP.Vaccinationandtheevolu-tionaryecologyofhumanpapillomavirus[J].Vaccine,2008,269(3):25-30.[14]StanleyM,VillaLL.MonitoringHPVvaccination[J].Vaccine,2008,26(1):24-27.[15]HuangB,MaoCP,PengS,etal.RNAinterference-mediatedinvivosilencingoffasligandasastrategyfortheenhancementofDNAvac-cinepotency[J].HumGenTher,2008,19(8):763-773.[16]TsengCW,MonieA,TrimbleC,etal.Combinationoftreatmentwithdeathreceptor5-specificantibodywiththerapeuticHPVDNAvaccina-tiongeneratesenhanncedtherapeuticanti-tumoreffects[J].Vaccine,2008,26(34):4314-4319.[17]SwellDA,PanZK,PatersonY.Listeria-basedHPV-16E7vaccineslimitautochthonoustumorgrowthinatransgenicmousemodelforHPV-16transformedtumors[J].Vaccine,2008,26(41):5322-5327.[18]HungCF,MonieA,AlvarezRD,etal.DNAvaccinesforcervicalcancer:frombenchtobedside[J].ExpMolMed,2007,39(6):679-689.[19]BrothertonJM,GoldMS,KempAS,etal.Anaphylaxisfollowingquadrivalenthumanpapillomavirusvaccination[J].CMAJ,2008,179(6):525-533.[20]StuddifordJ,LambK,HorvathK,etal.Developmentofunilateralc