Dynamics of Polymorphism in a Malaria Vaccine Antigen at a Vaccine-Testing Site in Mali 英文参考文献.docVIP

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Dynamics of Polymorphism in a Malaria Vaccine Antigen at a Vaccine-Testing Site in Mali 英文参考文献.doc

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Dynamics of Polymorphism in a Malaria Vaccine Antigen at a Vaccine-Testing Site in Mali 英文参考文献

o PL SMEDICINE DynamicsofPolymorphisminaMalariaVaccine AntigenataVaccine-TestingSiteinMali Shannon L.Takala1,Drissa Coulibaly2,Mahamadou A.Thera2,Alassane Dicko2,David L.Smith3,Ando B.Guindo2, Abdoulaye K.Kone2,Karim Traore2,Amed Ouattara1,2,Abdoulaye A.Djimde2,Paul S.Sehdev1,Kirsten E.Lyke1, Dapa A.Diallo2,Ogobara K. Doumbo2,Christopher V.Plowe1* 1 Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 2 Malaria Research and Training Center, UniversityofBamako,Bamako,Mali,3FogartyInternationalCenter,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Funding:Thisstudywasfundedby NationalInstituteofAllergyand InfectiousDiseases(NIAID)Contract N01AI85346,NIAIDGrant U19AI065683,FogartyInternational Center(FIC)GrantD43TW001589 andtheUSAIDMalariaVaccine Program.Thefundershadnorolein studydesign,datacollectionand analysis,decisiontopublish,or preparationofthemanuscript. ABSTRACT Background Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-119) derivedfromthe3D7strainofPlasmodiumfalciparumarebeingtestedinclinicaltrialsinAfrica. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinctionbetweennaturalfluctuationsingeneticdiversityandvaccine-inducedselection. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. MethodsandFindings AcademicEditor:PieroL.Olliaro, WorldHealthOrganization, Switzerland Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encodingMSP-119 weregenotypedfrom1,363malariainfectionsexperiencedby100children whoparticipatedinaprospectivecohortstudyinMalifrom1999to2001.Thefrequenciesof14 MSP-119 haplotypeswerecomparedoverthecourseofthemalariatransmissionseasonforall three years, in three age groups, and in consecutive infections within individuals. While the