Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets 英文参考文献.docVIP

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Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets 英文参考文献.doc

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Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets 英文参考文献

AntigenicFingerprintingofH5N1AvianInfluenzaUsing ConvalescentSeraandMonoclonalAntibodiesReveals PotentialVaccineandDiagnosticTargets SurenderKhurana1,AmorsoloL.SuguitanJr.2,YonairaRivera1,CameronP.Simmons3 ,Antonio Lanzavecchia4,FedericaSallusto4,JodyManischewitz1,LisaR.King1,KantaSubbarao2,HanaGolding1* 1Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America, 2Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 3OxfordUniversityClinicalResearchUnit,HospitalforTropicalDiseases,HoChiMinhCity,Vietnam,4InstituteforResearchinBiomedicine,Bellinzona,Switzerland Abstract Background: Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protectiveimmuneresponsesagainstavianinfluenza.CharacterizingtheBcellresponsesinconvalescentindividualscould helpinthedesignoffuturevaccinesandtherapeutics. Methods and Findings: To address this need, we generated whole-genome–fragment phage display libraries (GFPDL) expressingfragmentsof15–350aminoacidscoveringalltheproteinsofA/Vietnam/1203/2004(H5N1).TheseGFPDLwere used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection.Thisapproachledtothemappingoftwobroadlyneutralizinghumanmonoclonalantibodieswithconformation- dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibodyepitopesinH5HA[(-10)-223],neuraminidasecatalyticsite,andM2ectodomain.Inaddition,forthefirsttimetoour knowledgeinhumans,weidentifiedstrongreactivityagainstPB1-F