Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine 英文参考文献.docVIP

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Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine 英文参考文献.doc

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ProtectiveAntibodyandCD8T-CellResponsestothePlasmodiumfalciparumCircumsporozoiteProteinInducedbyaNanoparticleVaccine英文参考文献

ProtectiveAntibodyandCD8+T-CellResponsestothe PlasmodiumfalciparumCircumsporozoiteProtein InducedbyaNanoparticleVaccine StephenA.Kaba1,MargaretE.McCoy1,TaisA.P.F.Doll2,ClaraBrando1,QinGuo1,DebleenaDasgupta1, YongkunYang2,ChristianMittelholzer3¤,RobertaSpaccapelo4,AndreaCrisanti5,PeterBurkhard2,6, DavidE.Lanar1* 1Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America, 2Institute of Materials Science, University of Connecticut, Storrs, Connecticut, United States of America, 3M.E. Mu¨ller Institute for Structural Biology, University of Basel, Basel, Switzerland, 4Department of ExperimentalMedicine,MicrobiologySection,UniversityofPerugia,Perugia,Italy,5ImperialCollegeLondon,London,UnitedKingdom,6DepartmentofMolecularand CellBiology,UniversityofConnecticut,Storrs,Connecticut,UnitedStatesofAmerica Abstract Background: The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effectivevaccineagainstthePlasmodiumfalciparumparasite.Aneffectivevaccinewillmostlikelyrequiretheinductionof + + antigenspecificCD8 andCD4 T-cellsaswellaslong-lastingantibodyresponsesallworkinginconcerttoeliminatethe infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proveneffectiveincontrolofaP.bergheiinfectioninarodentmodeltonowpresentB-andT-cellepitopesofthehuman malariaparasiteP.falciparuminaplatformcapableofbeingusedinhumansubjects. Methodology/PrincipalFindings:ToestablishthebasisforaSAPN-basedvaccine,B-andCD8+T-cellepitopesfromtheP. falciparumcircumsporozoiteprotein(PfCSP)andtheuniversalCD4T-helperepitopePADREwereengineeredintoaversatile small protein (,125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasiteofmiceexpressingthehumanmalariafull-leng