Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine 英文参考文献.docVIP

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Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine 英文参考文献.doc

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Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine 英文参考文献

EffectofAdjuvantsonResponsestoSkinImmunization byMicroneedlesCoatedwithInfluenzaSubunitVaccine WilliamC.Weldon1,VladimirG.Zarnitsyn2,E.SteinEsser1,MishaT.Taherbhai1, DimitriosG.Koutsonanos1,ElenaV.Vassilieva1,IoannaSkountzou1,MarkR.Prausnitz2, RichardW.Compans1* 1DepartmentofMicrobiologyandImmunologyandEmoryVaccineCenter,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica,2Schoolof ChemicalandBiomolecularEngineering,GeorgiaInstituteofTechnology,Atlanta,Georgia,UnitedStatesofAmerica Abstract Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; howeverthereislittleinformationontheeffectsofadjuvantsusingthisapproachforvaccination.Hereweinvestigatethe use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1mg of monovalentH1N1subunitvaccinealoneorwith1mgofimiquimodorpoly(I:C)individuallyorincombinationviacoated microneedlepatchesinsertedintotheskin.Poly(I:C)adjuvantedsubunitinfluenzavaccineinducedsimilarantigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod- adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-c cellular response. These responses correlated with improved protection compared to influenzasubunitvaccinealone,aswellasreducedviralreplicationandproductionofpro-inflammatorycytokinesinthe lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responsescomparedtovaccinealonesupportstheuseofTLR7ligandsasadjuvantsforskin-basedinfluenzavaccines. Citation: Weldon WC, Zarnitsyn VG, Esser ES, Taherbhai MT, Koutsonanos DG, et al. (2012) Effect of Adjuvants on Responses to Skin Immunization by MicroneedlesCo