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1、中華實(shí)驗(yàn)和臨床病毒學(xué)雜志2014年8月第28卷第4期ChineseJExpClinVirol，August2014，Vo1．28，No．4·245·．論著腸道病毒71型手足口病的疫苗篩選和觀察姚思敏，楊桂林，劉威龍，方木通，周伯平【摘要】目的篩選安全有效新型EV71候選疫苗，為將來EV71疫苗開發(fā)應(yīng)用奠定基礎(chǔ)。方法以重組蛋白VP1為疫苗設(shè)計(jì)靶點(diǎn)，不同候選疫苗包括滅活疫苗、DNA疫苗、VP1蛋白疫苗在0、2周、4周分別按照不同劑量和肌內(nèi)注射途徑免疫BALB／c雌性小鼠，在0、2周、4周、6周、8周、10周、16周分別采集小鼠尾
2、靜脈血，16周處死小鼠，收集小鼠脾臟細(xì)胞，檢測小鼠體液免疫和細(xì)胞免疫功能，篩選評價(jià)候選疫苗的療效和安全性。結(jié)果滅活病毒疫苗、VPIDNA質(zhì)粒疫苗、VP1蛋白疫苗免疫小鼠2周后IgG抗體滴度即開始升高，4周后明顯升高，8周后達(dá)高峰，至少維持16周以上；IgG亞類以IgG2a和IgGl為主。三種疫苗能誘導(dǎo)以-IFN和IL4為主的細(xì)胞免疫反應(yīng)。滅活疫苗療效優(yōu)于其他候選疫苗，未發(fā)現(xiàn)疫苗相關(guān)不良反應(yīng)。結(jié)論滅活病毒疫苗、VP1DNA質(zhì)粒疫苗、VP1蛋白疫苗均能誘導(dǎo)持久的特異性細(xì)胞免疫和中和抗體反應(yīng)，以滅活病毒疫苗療效較好，需要將來攻毒實(shí)
3、驗(yàn)可進(jìn)一步驗(yàn)證其免疫力?！局黝}詞】腸道病毒屬；手足口病Screeningofvaccinecandidatesforenterovirus71associatedhand，footandmouthdiseaseYaoSimin，y口Guilin，LiuWeilong，F(xiàn)angMutong，ZhouBoping．ShenzhenPeople’sHospital，Shenzhen518112，ChinaCorrespondingauthor：ynGuilin，Email：g1．yang@163．corn【Abstract】Obj
4、ectiveToScreenforsafeandeffectivevaccinecandidatesforEV71，provideatheoreticalbasisfordevelopmentofEV71vaccinesinthefuture．MethodsVP1geneofenteroviruswasusedtodesignatargetfordevelopmentofEVT1vaccines．Differentvaccinecandidates，includinginactivatedEV71vaccines，VP1pr
5、oteinvaccine，DNAvaccinesofdifferentdoses，wereusedtochallengefemaleBALB／cmicebyintramuscularinjectionatbaseline(0)，2weeks，4weeks，andcaudalveinbloodwascollectedat0，2，4，6，8，10，and16weeks，andBALB／cmiceweresacrificedandthespleencellswerecollectedfordetectionofbothhumora
6、limmunityandcellularimmunitytoevaluatetheefficacyandsafetyofthevaccinecandidates．ResultsIgGantibodytiterswereincreasedat2weeks．remarkablyincreasedat4weeks，reachedapeakat8weeks，atleastsustainedfor16weeksduringthewholeobservationperiod，subtypesofIgG1andIgG2awerethema
7、jorcomponent．ThethreevaccinescouldinducecellularimmunitycharacterizedbyEV71specific一IFNandIL一4production．OurresultsindicatedthatinactivatedEV71vaccinewassuperiortotheothervaccinecandidates．ConclusionsInactivatedEV71vaccines．VP1proteinvaccine．DNAvaccinescaninducebot
8、hstrongandsustainablehumoralandcellularimmunitiesinchallengedmice．a(chǎn)ndtheinactivatedEV71vaccineiSsuperiortotheothervaccinecandidates，whichneedstob
