冠状病毒Coronavirusl论文-2005 Elicitation of Immunity in Mice After Immunization with the S2 Subunit of the Severe Acute Respiratory Syndrome Cor.pdf

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1、DNAANDCELLBIOLOGYVolume24,Number8,2005©MaryAnnLiebert,Inc.Pp.510–515ElicitationofImmunityinMiceAfterImmunizationwiththeS2SubunitoftheSevereAcuteRespiratorySyndromeCoronavirusYINGJUNGUO,1SHUHANSUN,1KAIYUWANG,1SHUZHANG,1WEIJIAZHU,1andZECHEN2,3ABSTRACTTheS2domainofthesevereacuteresp

2、iratorysyndromecoronavirus(SARS-CoV)spike(S)proteinisre-sponsibleforfusionbetweenvirusandtargetcellmembranes,andisexpectedtobeimmungenic.Inthisstudy,weinvestigatedtheimmuneresponsesagainsttheS2subunitinBALB/cmice,whichwerevaccinatedeitherwithplasmidDNAencodingtheS2domain(residues

3、681–1120),therecombinantS2fragment(residues681–980)inincompleteFreund’sadjuvant,orwithinactivatedSARS-CoV.Theincreasednumberofspecificcytotoxiccells(CTLs)andthehightiterofspecificantibodyshowedstimulationofbotharmsoftheimmunesysteminthesegroups.TheshiftincytokinessuggestedthatTh1

4、–polarizedimmuneresponsewasinducedbyplasmidpCoVS2,meanwhiletheTh2-dominantresponsewasinducedbyrecombinantS2fragmentandin-activatedvaccine.However,thetiterofneutralizingantibodieswasonlydetectableinmiceimmunizedwithinactivatedvirus,butnotwithpCoVS2plasmid.Takentogether,theS2domain

5、couldinducespecificcellu-larimmuneresponseandahighleveloftotalIgGbutlittleneutralizingantibodiesagainstinfectionbySARS-CoV.INTRODUCTIONproteincouldpotentiallyserveasthebestantigen/immunogen(Flemingetal.,1983;Ontiverosetal.,2003).Thespike(S)ARS-COV,AHIGHLYAGGRESSIVEPATHOGENbecamee

6、videntglycoproteinofthecoronavirusisalargeandmultifunctionalSintheGuangdongprovinceofsouthernChinainlate2002,proteinthatplayscrucialrolesinmediatingviralinfectionandisthecausativeagentofanatypical,highlycontagiousres-throughreceptorbindingandspecificmembranefusion.Thepiratorydise

7、asethathasoccuredin32countriesin2003,andglycoproteinhastwofunctionalregions.S1isthereceptorbind-hasresultedinapproximately8400casesand900deaths.Theingsiteanddefinesthehostrangeofthevirus,andS2isatrans-virusbelongstoadiversegroupoflarge(160–170kDa),en-membranesubunitthatmediatesfu

8、sionbetweentheviralandveloped,positive-s