疫苗佐剂最新研究进展-周洋

ChineseJournalofNewDrugs2013221342013221“”2012ZX09302-001。[e-mail]。。[e-mail]。[e-mail]。··100176。。、。。R186R979．9A1003－3734201301－0034－09RecentdevelopmentinvaccineadjuvantresearchZHOUYangGENGXing-chaoWANGJu-fengLIBoNationalCenterforSafetyEvaluationofDrugsNationalInstituteforFoodandDrugControlBeijing100176ChinaAbstractVaccineadjuvantcanenhanceadaptiveimmuneresponsestoantigenswhichisveryimportantinresearchanddevelopmentofnovelvaccines．Inrecentyearsmoreandmorenovelvaccineadjuvanthasbeendeveloped．Inthisarticlewesummarizedthecurrentpracticeandfutureperspectivesfordifferentadjuvantinclu-dingthepotentialapplicationsactionofmechanismtheeffectsonimmunesystemtheclinicalefficiencyandad-verseeventsandthehighlightsonadjuvantresearchanddevelopment．Inadditiontoidealadjuvantwealsopayattentiontothesafetyissueofvaccineadjuvant．Furtherunderstandingabouttheadjuvantmodeofactionandestab-lishingreliablemodelhelpinassessingvaccinesafetythoroughlyandalleviatingpublichealthconcern．Keywordsadjuvantvaccineimmuneresponseactionofmechanismsafetyevaluation1、。80。1。FIAMontanide65Adjuvant65Li-povant2。、、。、3。QS-21HIV-P2。。13－4。MF59AS03AS04Adju-ChineseJournalofNewDrugs2013221352013221vantSystem04HBVHPV4。。TollTLR。1①FDA②③①②③④⑤Th2①②③APC④①②IgE。③TMF59①8085②CD11b+MH-CII+DCTh2①②③AS03E80①②③AS04MPLLPSTLR4NFkBAPCTh1HBVHPV①②③CpG-ODNTLR9IC31ITh1HBVHCVPolyICdsRNATLR3NKCD+8T、ISCOMSQuilAQS21。ICTL①②MHCICD8CTLHAV①②③①②③④①②③APC①②①②。11．1TLR1．1．1。。4。Caspase-1IL-1βIL-185。NLRP3NACHT-LRR-PYD-containingprotein3ChineseJournalofNewDrugs20132213620132216。NLRP3DCsIL-1βTh2。NLRP3NLRP3TB。NLRP3。HAV、HBV、HPV、DT、BHIB。T。、。3。。1．1．2MF59AS03MF59AS03。MF597、CD11b+MHCII+。MF59DCs。Pen-traxin3Ptx3JunBMF59DCs7。MF59Th28Th1。MF59H5N1CD+4T9。MF59TMGLPMF59TM10。。MF59、。。MF59。MF59351997。FluadRMF59TM10。MF59HI4。AS03MF592009H1N14。H1N1H5H511。MF59AS03H5412。MF5910500013。MF593000。MF59。1．1．3ISCOMS、、VLP。ISCOMS、、。ISCOMATRIX。ISCOM-ATRIXIgA2。ISCOMsPRRDCsDCsT17。ISCOMsMHCICD+8CD+4T。ISCOMsDNA17。ISCOMsIgA。、15。-。。Quil-A。QS-218、HIV、、HIP、HBV、15。。ChineseJournalofNewDrugs2013221372013221MHCICD+8T3。CAFTDBCAF0116。I。CAF01TBAPCsT。、。。VLP2。VLPDCs3。HB-sAgVLP。VLPFDA2。VLPDNA3。PLGA。1。。PLGNLRP31。“”。PLA。Kreb's。PLA15。。TTDT8。。。8。。chitosan3。IgG。chitosan。PLGAPLAchitosanHBsAg。1．1．4。。-GM-CSFAPC。CM-CSF2。。。15。IL-12IgG2aIgA8。IL-12。Th1AIDS15。IL-1OVAIgGIgA8。IL-1。DNADNA2。。1．2TLRTLR。TLRPAMPLPSCpGTLR。TLR2。ChineseJournalofNewDrugs20132213820132212TLRsTLRTLR1/IITh1NKTLR2MDPIITh1NKTLR3dsRNAPolyICNKTLR460/70LPSRVSMDPMPLTh1MPLHBVHPVTLR5Th1CTLTLR6、MALP-2MALP-3Th1NKTLR7、ssRNAR-848ssRNATh1CTLTLR8、ssRNAR-848ssRNATh1CTLTLR9CpGDNADNA-IgGCpG-ODNsTh1CTLNK1．2．1TLR4MPLAS04MPL2。MPLLPS17Toll4TLR4517MPLTLR4。LPSTLR4MyD88-TIRAPTRIF-TRAMMPLTRIF-TRAMMPL18。AS045TLR4APCAPC。APCT。TB。AS04APC17。AS0424h5。AS04NF-κB。NF-κB195。AS04HPVMPLDCs5。AS04MPLBMDCsAS04DCsCD+86。ovalbuminOVAOVADCsOVAMPLOVAAS04DCsCD+4T。AS04、AS0430。、。MPL17。AS0416/18HIV-16/18HBV。3Ⅲ17。HPV-16/18ⅢHPV11717。HBVHBV17。MPLTLR45AS04TLR4DCs。TLR4AS04。ChineseJournalofNewDrugs2013221392013221IFN-α17。IFN-αSLE17。AS04IFN-α5。AS04AS04。1．2．2TLR9CpGDNATLR9DNAPRRAPCsBpDCsDNA14。CpGDNACpG。CpGISSTLR94。CpG-ODNCpG18～2514。CpG-ODNTLR9DCsBNKTTLR9Th120。CpG-ODN33BCTh1CD+4CD+8T。ACpG-ODNCD+8TIgG/IgG2aT。3CpG-ODNAPCApDCNKIFN-αIFN-γBBTh1CD+4TCCpGpDCNKBCpG20。CpG-ODNCpG-ODNCD80CD8621。BCD80CD86TT。CpGIL-12aIL-12bIL-1012hIL-12IL-4IL-5IFN-γmRNA21。CpGMHCIMHCII。CpGIL-12p40CCL5CCL2CXCL17。CpG、。CpG-ODN、、。CpG-ODNCpG-ODN。1018ISSODNB。4。IC31KLKL5KLKODN1a4。TLR9MyD88Th1。IC31。KLKODN。IC31TBTBAg85B-ESAT-6IC314。IC31。Ag85B-ESAT-6/IC31。1．2．3TLR3PolyICpolyinsin-ic-polycytidylicacidPolyICRNAPRRsdsR-NATLR3RLR-1RIG-15MDA-5。TLR3TRIFRLRIFN-β-1IFN-βpromoterstimulatory-121。DCsTLR3IL-12IMHCII。IL-12Th1CTLIFN-γ19。MDA-5IIFN。IChineseJournalofNewDrugs2013221402013221TB。dsRNANKCD+8T22。PolyIC、Th123。Longhi24DCHIVgagTLRPolyICIIFNCD+4T。IIFNDCTHIV-gagTh124。MHCI、CD+8T。PolyICCD+8T25CD+8T。PolyICAPC。PolyIC22。PolyICRNA23。26。PolyIC。、PolyIC。PolyIC12UAIDS27。、、、、。1．2．4TLR2TLR2。MDP。MDPMDPMDP2。-2MALP-2TLR2。MALP-2TLR2-TLR6MyD88NF-κBAPCs。BTLR2TLR6。T/BMALP-2TBBT8。1．2．5TLR5TTLR5。。TLRTh1、Th2Th1。TLR5TLRMyD8814。1．2．6TLR7TLR8ssRNATLR7TLR8。TLR7、TLR8TLR7/8。TLR7TLR8MyD88。TLR7TLR8。TLR7-TLR8DCsBTh114。TLR84。TLR8APCTh1TNF-αIL-12。TLR3/8TLR4/8DCsIL-12p70Th1。TLR74。TLR。22．1HIV。28。。ChineseJournalofNewDrugs2013221412013221。。。。。CpGTLRTα-28。2．2/2。TLR4。AS02MPLQS21。RTSSAS0237%。RTSS。AS02MAGE-A3CD+4T。APspA。wPPspA。PspA。PspAIgGIgA。IgG1/IgG2awPTh1Th1Th218。CpG-ODNMDP18。。。、。AS0428。2．328。PRR。PRRTLRsNodNLRsIRLRs。PRRs。“”。。。TLR4MPLTLR9。TLRTLRTLR。PRRsRLRsNLRsNL-RP3。α-NKT28。2．413。TLR。TLR。。3。。。。ChineseJournalofNewDrugs2013221422013221。。。1SCHIJNSVELAVELLEEC．TrendsinvaccineadjuvantsJ．ExpertRevVaccines2011104539－550．2AGUILARJCRODRIGUEZEG．VaccineadjuvantsrevisitedJ．Vaccine200725193752－3762．3SIVAKUMARSMSAFHIMMKANNADASANMetal．Vac-cineadjuvants-currentstatusandprospectsoncontrolledreleaseadjuvancityJ．SaudiPharmaceuticalJ2011194197－206．4MBOWMLDEGREGORIOEVALIANTENMetal．NewadjuvantsforhumanvaccinesJ．CurrOpinImmunol2010223411－416．5DIDIERLAURENTAMMORELSLOCKMANLetal．AS04a