Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a Mucosal Immune Response 英文参考文献.docVIP

OuterMembraneVesiclesofPorphyromonasgingivalis ElicitaMucosalImmuneResponse RyomaNakao1,HidekiHasegawa2,KuniyasuOchiai3,ShogoTakashiba4,AkiraAinai2,MakotoOhnishi1, HaruoWatanabe1,HidenobuSenpuku1* 1DepartmentofBacteriologyI,NationalInstituteofInfectiousDiseases,Tokyo,Japan,2DepartmentofPathology,NationalInstituteofInfectiousDiseases,Tokyo,Japan, 3DepartmentofMicrobiology,NihonUniversity,Tokyo,Japan,4DepartmentofPathophysiology-PeriodontalScience,OkayamaUniversityGraduateSchoolofMedicine, Okayama,Japan Abstract We previously reported that mutation of galE in Porphyromonas gingivalis has pleiotropic effects, including a truncated lipopolysaccharide (LPS)O-antigenanddeglycosylationof theoutermembrane proteinOMP85homolog.Inthepresent study,furtheranalysisofthegalEmutantrevealedthatitproducedlittleornooutermembranevesicles(OMVs).Usingthree mouseantiseraraisedagainstwholecellsoftheP.gingivaliswildtypestrain,weperformedELISAstoexaminethereactivity oftheseantiserawithwholecellsofthewildtypeorthegalEmutant.Allthreeantiserahadsignificantlylowerreactivity against the galE mutant compared to wild type. OMVs, but not LPS, retained the immunodominant determinant of P. gingivalis,asdeterminedbyELISAs(withwildtypeLPSorOMVsasantigen)andabsorptionassays.Inaddition,weassessed the capacity of OMVs as a vaccine antigen by intranasal immunization to BALB/c mice. Synthetic double-stranded RNA polyriboinosinicpolyribocytidylicacid[Poly(I:C)],anagonistofToll-likereceptor3(TLR3),wasusedasthemucosaladjuvant. Vaccination with OMV elicited dramatically high levels of P. gingivalis-specific IgA in nasal washes and saliva, as well as serumIgGandIgA.Inconclusion,theOMVsofP.gingivalishaveanimportantroleinmucosalimmunogenicityaswellasin antigenicity. We propose that P. gingivalis OMV is an intriguing immunogen for development of a periodontal disease vaccine. Citation: Nakao R, Hasegawa H, Ochiai K, Takashiba S, Ainai A, et al. (2011) Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a