Evaluation of Wuchereria bancrofti GST as a Vaccine Candidate for Lymphatic Filariasis 英文参考文献.docVIP

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Evaluation of Wuchereria bancrofti GST as a Vaccine Candidate for Lymphatic Filariasis 英文参考文献.doc

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Evaluation of Wuchereria bancrofti GST as a Vaccine Candidate for Lymphatic Filariasis 英文参考文献

EvaluationofWuchereriabancroftiGSTasaVaccine CandidateforLymphaticFilariasis AnandharamanVeerapathran1,2,GajalakshmiDakshinamoorthy2,MunirathinamGnanasekar1 ,Maryada VenkataRamiReddy2,RamaswamyKalyanasundaram1* 1DepartmentofBiomedicalSciences,UniversityofIllinoisCollegeofMedicineatRockford,Rockford,Illinois,UnitedStatesofAmerica,2DepartmentofBiochemistry, MahatmaGandhiInstituteofMedicalSciences,Sevagram,Maharashtra,India Abstract Background: Lymphatic filarial parasites survive within the lymphatic vessels for years despite the complex immune environment surrounding them. Parasites possibly accomplish this by adopting various immunomodulatory strategies, whichincludereleaseofglutathione-S-transferases(GSTs)thatcounteracttheoxidativefreeradicalsproducedbythehost. SinceGSTsproducedbyparasitesappeartobecriticalforthesurvivalofparasitesinthehost,severalstudiesevaluatedthe potentialofparasiteGSTsasvaccinecandidatesespeciallyagainstschistosomiasis,fascioliasisandSeteriacervi .However, vaccinepotentialofGSTsoflymphaticfilarialparasiteshasnotbeenevaluatedbefore. Methods/PrincipalFindings:Inthepresentstudy,theGSTgenewasclonedfromthethirdstagelarval(L3)cDNAlibrariesof Wuchereriabancrofti,andrecombinantGST(WbGST)wasexpressedandpurified.Serumsamplesfromindividualslivingin anendemic area wereanalyzed for theirreactivity with rWbGST.These findings showedthat sera fromendemic normal individuals(EN)carrysignificantlevelsofanti-WbGSTIgGantibodiescomparedtosubjectswhoaremicrofilaraemic(Mf)or showsymptomsofclinicalpathology(CP).Isotypeanalysisoftheanti-WbGSTIgGantibodiesshowedapredominanceof IgG1andIgG3antibodiesinENindividuals.SubsequentfunctionalanalysisoftherWbGSTshowedthattherWbGSTprotein retainedtheenzymaticactivityofGSTandtheantibodiesinENseracouldinhibitthisenzymaticactivity.Similarresultswere obtainedwhenanti-rWbGSTantibodiesraisedinmicewereusedintheneutralizationassay.BrugiamalayiGSTandWbGST show significant sequence similarity. Therefore, to evaluate the vaccine potential