Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines 英文参考文献.docVIP

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Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines 英文参考文献.doc

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Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines 英文参考文献

PentamersNotFoundintheUniversalProteomeCan EnhanceAntigenSpecificImmuneResponsesand AdjuvantVaccines AmiPatel1,2¤,JessicaC.Dong1,3,BrettTrost4,JasonS.Richardson1,SarahTohme1,ShawnBabiuk3,5, AnthonyKusalik4,SamK.P.Kung3,GaryP.Kobinger1,2,3* 1SpecialPathogensProgram,NationalMicrobiologyLaboratory,PublicHealthAgencyofCanada,Winnipeg,Canada,2DepartmentofMedicalMicrobiology,Universityof Manitoba,Winnipeg,Canada,3DepartmentofImmunology,UniversityofManitoba,Winnipeg,Canada,4DepartmentofComputerScience,UniversityofSaskatchewan, Saskatoon,Canada,5NationalCentreforForeignAnimalDisease,CanadianFoodInspectionAgency,Winnipeg,Manitoba,Canada Abstract Certainshortpeptidesdonotoccurinhumansandarerareornon-existentintheuniversalproteome.Antigensthatcontain rareaminoacidsequencesareingeneralhighlyimmunogenicandmayactivatedifferentarmsoftheimmunesystem.We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKBdatabase.Experimentalobservationsindicatedthatrareandsemi-common5-mersgeneratedstrongercellular responsesincomparisonwithcommon-occurringsequences.Wehypothesizedthatthebiologicalprocessresponsiblefor this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccinedevelopment.Initially,twelverare5-mers,9-mers,and13-merswereincorporatedinframeattheendofanH5N1 hemagglutinin(HA)antigenandexpressedfromaDNAvaccine.Thepresenceofsome5-merpeptidesinducedimproved immuneresponses.Addingone5-merpeptideexogenouslyalsoofferedimprovedclinicaloutcomeand/orsurvivalagainst alethalH5N1orH1N1influenzaviruschallengeinBALB/cmiceandferrets,respectively.Interestingly,enhancedanti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency wasobserved withenhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or