Adjuvanted Influenza Vaccine Administered Intradermally Elicits Robust Long-Term Immune Responses that Confer Protection from Lethal Challenge 英文参考文献.docVIP

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Adjuvanted Influenza Vaccine Administered Intradermally Elicits Robust Long-Term Immune Responses that Confer Protection from Lethal Challenge 英文参考文献.doc

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Adjuvanted Influenza Vaccine Administered Intradermally Elicits Robust Long-Term Immune Responses that Confer Protection from Lethal Challenge 英文参考文献

AdjuvantedInfluenzaVaccineAdministered IntradermallyElicitsRobustLong-TermImmune ResponsesthatConferProtectionfromLethalChallenge MariadelP.Martin1,ShagunaSeth2,DimitriosG.Koutsonanos1,JoshyJacob1,RichardW.Compans1*, IoannaSkountzou1* 1DepartmentofMicrobiologyandImmunologyandEmoryVaccineCenter,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica,2MDRNA, Inc.,Bothel,Washington,UnitedStatesofAmerica Abstract Background: Therespiratory illnessescausedby influenzavirus canbe dramaticallyreducedbyvaccination. Thecurrent trivalent inactivated influenza vaccine is effective in eliciting systemic virus-specific antibodies sufficient to control viral replication.However,influenzaprotectiongeneratedafterparenteralimmunizationcouldbeimprovedbytheinductionof mucosalimmuneresponses. Methodology/Principal Findings: Transcutaneous immunization, a non-invasive vaccine delivery method, was used to investigate the quality, duration and effectiveness of the immune responses induced in the presence of inactivated influenzavirusco-administeredwithretinoicacidoroleicacid.Weobservedanincreasedmigrationofdendriticcellstothe draininglymphnodesafterdermalvaccination.Herewedemonstratethatthisrouteofvaccinedeliveryincombinationwith certain immunomodulators can induce potent immune responses that result in long-term protective immunity. Additionally, mice vaccinated with inactivated virus in combination with retinoic acid show an enhanced sIgA antibody response,increasednumberofantibodysecretingcellsinthemucosaltissues,andprotectionfromahigherinfluenzalethal dose. Conclusions/Significance: The present study demonstrates that transdermal administration of inactivated virus in combination with immunomodulators stimulates dendritic cell migration, results in long-lived systemic and mucosal responsesthatconfereffectiveprotectiveimmunity. Citation:MartinMdP,SethS,KoutsonanosDG,JacobJ,CompansRW,etal.(2010)AdjuvantedInfluenzaVaccineAdministeredIntradermallyElicitsRobustLong- Term