亚单位疫苗研究进展_李超.pdf

亚单位疫苗研究进展_李超.pdf

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时间:2020-03-07

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1、第十届全国免疫学学术大会疗研究提供一定的研究基础和依据。乙型肝炎病毒,清除性抗体,免疫缺陷小鼠(ID号:519)DNAvaccineencodingHantavirusGn,targetedtoMIICbytraffickingmoleculeLAMP,significantlyenhancesspecificimmuneresponses1,21,21,21,211JinpengZhang,ShaoboXiao,PeihanHe,YunweiWang,DongboJiang,KunYang1.DepartmentofImmunolog

2、y,theFourthMilitaryMedicalUniversity2.BrigadeofCadet,theFourthMilitaryMedicalUniversityLysosome-associatedmembraneprotein(LAMP)cantargetandbindtoendosome/lysosome,oneofthemostimportantcomponentsoftheMHCclassII-processingcompartment(MIIC)intheexogenousantigen-processingpa

3、thway.LAMPtraffickinggreatlyenhancetheimmuneresponsebecauseendogenousantigencantakeadvantageofLAMPbeingdirect-lycarriedintoMIIC,activatingCD4+helperTcellsforeffectiveimmueresponseandlong-termimmunememory.HantavirusglycoproteinN-terminal,namedGn,couldinduceneutralizingant

4、ibodyproductionwithalowserumtiterasnaturalinfection.ToanalyzetheinfluenceofLAMPonHantaanvirus(HTNV)GnvaccinepotencyanddevelopanoveleffectivevaccineagainstHTNV,weconstructedthreeeukaryoticvectorsasnakedDNAvaccinenamedpVAX-Gn,pVAX-LAMPandpVAX-LAMP/Gn,respectively.Balb/cmic

5、ewereimmunizedwiththoseplasmids,thespecifichumor-alandcellularresponseselicitedagainstHTNVGnweremeasuredbyELISA,cytotoxicityassaysandELISPOTassay(IFN-γ).Tomeasuretheprotectiveefficacy,viruschallenginginvivoandneutralizingantibodyvalencewereconductedbyviralloaddetection(q

6、RT-PCRandsandwichELISA)andthecellmicrocultureneutralizationtest.WefoundthatHTNVGnshowedastrongimmunogenicitytoelicitbothhumoralandcellularresponseswithLAMPasachimera.Comparedwiththecurrentprophylacticinactivevaccine,pVAX-LAMP/Gnshowedastrongercellularresponse.Beingworthr

7、aising,asignificantlongtermmemoryreponsewasobservedonlyfromthegroupofpVAX-LAMP/Gn.HistopathologicalanalysisbyHEstainingdemonstratedthatpVAX-LAMP/Gnwasnotharmful.ResultsofprotectionassayinvivoindicatedthattheimmuneresponseestablishedwasHTNVspecificandprotective.Thesefindi

8、ngsnotonlydemonstratedthattheLAMPasatraffickingmoleculecanintroduceGntoMHCIIpresentingpathwayandsignifi

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