Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovani Infection in Susceptible BALBc Mice 英文参考文献.docVIP

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Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovani Infection in Susceptible BALBc Mice 英文参考文献.doc

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Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovani Infection in Susceptible BALBc Mice 英文参考文献

SingleDoseNovelSalmonellaVaccineEnhances ResistanceagainstVisceralizingL.majorandL.donovani InfectioninSusceptibleBALB/cMice JulianeSchroeder1¤,NajmeeyahBrown2,PaulKaye2,ToniAebischer1,3* 1InstituteofImmunologyandInfectionResearch,UniversityofEdinburgh,Edinburgh,UnitedKingdom,2CentreforImmunologyandInfection,HullYorkMedicalSchool andDepartmentofBiology,UniversityofYork,York,UnitedKingdom,3RobertKoch-Institute,Berlin,Germany Abstract Visceral leishmaniasis is a major neglected tropical disease, with an estimated 500,000 new cases and more than 50,000 deathsattributabletothisdiseaseeveryyear.Drugtherapyisavailablebutcostlyandresistanceagainstseveraldrugclasses hasevolved.Despiteallefforts,nocommercial,letaloneaffordable,vaccineisavailabletodate.Thus,thedevelopmentof cost effective, needle-independent vaccines is a high priority. Here, we have continued efforts to develop live vaccine carriersbasedonrecombinantSalmonella.WeusedaninsilicoapproachtoselectnovelLeishmaniaparasiteantigensfrom proteomicdatasets,withselectioncriteriabasedonproteinabundance,conservationacrossLeishmaniaspeciesandlow homologytohostspecies.FivechosenantigensweredifferentiallyexpressedonthesurfaceorinthecytosolofSalmonella typhimuriumSL3261.Atwo-stepprocedurewasdevelopedtoselectoptimalSalmonellavaccinestrainsforeachantigen, basedonbacterialfitnessandantigenexpressionlevels.WeshowthatvaccinestrainsofSalmonellaexpressingthenovel Leishmania antigensLinJ08.1190 andLinJ23.0410 significantlyreducedvisceralisation ofL.majorandenhancedsystemic resistance against L.donovani in susceptible BALB/c mice. The resultsshow that Salmonella arevalidvaccine carriersfor inducingresistanceagainstvisceralleishmaniasisbutthattheirusemaynotbesuitableforallantigens. Citation: Schroeder J, Brown N, Kaye P, Aebischer T (2011) Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovaniInfectioninSusceptibleBALB/cMice.PLoSNeglTropDis5(12):e1406.doi:10.1371/journal.pntd.0001406