Protection against Chlamydia Promoted by a Subunit Vaccine (CTH1) Compared with a Primary Intranasal Infection in a Mouse Genital Challenge Model 英文参考文献.docVIP
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Protection against Chlamydia Promoted by a Subunit Vaccine (CTH1) Compared with a Primary Intranasal Infection in a Mouse Genital Challenge Model 英文参考文献
ProtectionagainstChlamydiaPromotedbyaSubunit
Vaccine(CTH1)ComparedwithaPrimaryIntranasal
InfectioninaMouseGenitalChallengeModel
AnjaWeinreichOlsen*,MichaelTheisen¤,DennisChristensen,FrankFollmann,PeterAndersen*
ChlamydiaandAdjuvantResearch,DepartmentofInfectiousDiseaseImmunology,StatensSerumInstitut,Copenhagen,Denmark
Abstract
Background:ThechlamydialproteinsCT443(OmcB)andCT521(rl16)havepreviouslybeenidentifiedashumanBand/orT
celltargetsduringachlamydialinfectioninhumans.Herewecomparetheprotectiveeffectormechanismpromotedbya
fusionproteincomposedofCT521andCT443(CTH1)withaprimaryintranasalChlamydiamuridaruminfectionknownto
providehighlevelsofprotectionagainstagenitalchlamydialchallenge.
Methodology/Principal Findings: The fusion protein CTH1, adjuvanted with a strong Th1 inducing cationic adjuvant
(CAF01),significantlyreducedthebacterialsheddingcomparedtoacontrolgroupinbothaC.trachomatisSerovarDandC.
muridarumchallengemodel.TheCTH1/CAF01vaccinewasfoundtoinducepolyfunctionalTcellsconsistingofTNFa/IL-2
andTNFa/IL-2/IFN-cpositivecellsandhightitersofCTH1specificIgG2aandIgG1.Bydepletionexperimentstheprotection
+
intheC.muridarumchallengemodelwasdemonstratedtobemediatedsolelybyCD4 Tcells.Incomparison,anintranasal
infectionwithC.muridaruminducedaTcellresponsethatconsistedpredominantlyofTNFa/IFN-cco-expressingeffector
+
CD4 T cells and an antibody response consisting of C. muridarum specific IgG1, IgG2a but also IgA. This response was
associatedwithahighlevelofprotectionagainstchallenge—aprotectionthatwasonlypartiallydependentonCD4 Tcells.
+
Furthermore, whereas the antibody response induced by intranasal infection was strongly reactive against the native
antigensdisplayedinthechlamydialelementarybody,onlylowlevelsofantibodiesagainstthispreparationwerefound
afterCTH1/CAF01immunization.
Conclusions/Significance: Our data demonstrate that CTH1 vaccination promotes a CD4+ T cell dependent protective
response but compared with intranasal C. muridarum infection lack
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