Elderly Subjects Have a Delayed Antibody Response and Prolonged Viraemia following Yellow Fever Vaccination A Prospective Controlled Cohort Study 英文参考文献.docVIP

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Elderly Subjects Have a Delayed Antibody Response and Prolonged Viraemia following Yellow Fever Vaccination A Prospective Controlled Cohort Study 英文参考文献.doc

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Elderly Subjects Have a Delayed Antibody Response and Prolonged Viraemia following Yellow Fever Vaccination A Prospective Controlled Cohort Study 英文参考文献

ElderlySubjectsHaveaDelayedAntibodyResponseand ProlongedViraemiafollowingYellowFeverVaccination: AProspectiveControlledCohortStudy AnnaH.Roukens1*,DariusSoonawala1,SimoneA.Joosten1,Adrie¨tteW.deVisser1,XiaohongJiang2, KeesDirksen3,MarjoleindeGruijter4,JaapT.vanDissel1,PeterJ.Bredenbeek2,LeoG.Visser1 1DepartmentofInfectiousDiseases,LeidenUniversityMedicalCenter,Leiden,TheNetherlands,2DepartmentofMedicalMicrobiology,LeidenUniversityMedicalCenter, Leiden,TheNetherlands,3MunicipalHealthCenterHollandsMidden,TheHague,TheNetherlands,4MunicipalHealthCenterLeiden,Leiden,TheNetherlands Abstract Background:Yellowfevervaccination(YF-17D)cancauseseriousadverseevents(SAEs).ThemechanismoftheseSAEsis poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune responsetoyellowfevervaccinedevelopsmoreslowlyinelderlythaninyoungersubjects. Method: We vaccinated young volunteers (18–28yrs, N=30) and elderly travelers (60–81yrs, N=28) with YF-17D and measuredtheirneutralizingantibodytitersandplasmaYF-17DRNAcopynumbersbeforevaccinationand3,5,10,14and 28daysaftervaccination. Results:Tendaysaftervaccinationseroprotectionwasattainedby77%(23/30)oftheyoungparticipantsandby50%(14/ 28)oftheelderlyparticipants(p=0.03).Accordingly,theGeometricMeanTiterofyoungerparticipantswashigherthanthe GMToftheelderlyparticipants.Atday10thedifferencewas+2.9IU/ml(95%CI1.8–4.7,p=0.00004)andatday14+1.8IU/ ml(95%CI1.1–2.9,p=0.02,usingamixedlinearmodel.Viraemiawasmorecommonintheelderly(86%,24/28)thaninthe youngerparticipants(60%,14/30)(p=0.03)withhigherYF-17DRNAcopynumbersintheelderlyparticipants. Conclusions:Wefoundthatelderlysubjectshadadelayedantibodyresponseandhigherviraemialevelsafteryellowfever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuatedvirustocausehigherviraemialevelswhichmayincreasetheriskofdevelopingSAEs.Thismaybeonepiecein thepuzzleofthepathophysiologyofYEL-AVD. TrialRegi