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Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2 英文参考文献.docVIP

Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2 英文参考文献.doc

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Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2 英文参考文献

EnhancedProtectiveEfficacyofaChimericFormofthe SchistosomiasisVaccineAntigenSm-TSP-2 MarkS.Pearson1,DarrenA.Pickering1,HenryJ.McSorley1,JeffreyM.Bethony2,LeonTribolet1, AnnetteM.Dougall1,PeterJ.Hotez3,AlexLoukas1* 1Queensland Tropical Health Alliance and School of Public Health and Tropical Medicine, James Cook University, Cairns, Queensland, Australia, 2Department of Microbiology,ImmunologyandTropicalMedicine,GeorgeWashingtonUniversity,WashingtonD.C.,UnitedStatesofAmerica,3DepartmentofPediatricsandMolecular Virology and Microbiology, and National School of Tropical Medicine, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, Baylor CollegeofMedicine,Houston,Texas,UnitedStatesofAmerica Abstract Thelargeextracellularloop oftheSchistosoma mansonitetraspanin, Sm-TSP-2, whenfusedtoathioredoxin partnerand formulatedwithFreund’sadjuvants,hasbeenshowntobeanefficaciousvaccineagainstmurineschistosomiasis.Moreover, Sm-TSP-2isuniquelyrecognisedbyIgG1andIgG3fromputativelyresistantindividualsresidentinS.mansoniendemicareas inBrazil.Inthepresentstudy,weexpressedSm-TSP-2athighyieldandinsolubleforminE.coliwithouttheneedfora solubilityenhancingfusionpartner.WealsoexpressedinE.coliachimeracalledSm-TSP-2/5B,whichconsistedofSm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associatedwithincreasedproductionofanti-Sm-TSP-2antibodiesandIL-4,IL-10andIFN-cfromspleencellsofvaccinated animals.Serafrom666individualsfromBrazilwhowereinfectedwithS.mansoniwerescreenedforpotentiallydeleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein

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