Evaluation of TcpF-A2-CTB Chimera and Evidence of Additive Protective Efficacy of Immunizing with TcpF and CTB in the Suckling Mouse Model of Cholera 英文参考文献.docVIP

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Evaluation of TcpF-A2-CTB Chimera and Evidence of Additive Protective Efficacy of Immunizing with TcpF and CTB in the Suckling Mouse Model of Cholera 英文参考文献.doc

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Evaluation of TcpF-A2-CTB Chimera and Evidence of Additive Protective Efficacy of Immunizing with TcpF and CTB in the Suckling Mouse Model of Cholera 英文参考文献

EvaluationofTcpF-A2-CTBChimeraandEvidenceof AdditiveProtectiveEfficacyofImmunizingwithTcpFand CTBintheSucklingMouseModelofCholera GregoryA.Price¤,RandallK.Holmes* DepartmentofMicrobiology,UniversityofColoradoSchoolofMedicine,Aurora,Colorado,UnitedStatesofAmerica Abstract The secreted colonization factor, TcpF, which is produced by Vibrio cholerae 01 and 0139, has generated interest as a potential protective antigen in the development of a subunit vaccine against cholera. This study evaluated immunogenicity/protectiveefficacyofaTcpFholotoxin-likechimera(TcpF-A2-CTB)followingintraperitonealimmunization compared to TcpF alone, a TcpF+CTB mixture, or CTB alone. Immunization with the TcpF-A2-CTB chimera elicited significantlygreateramountsofanti-TcpFIgGthanimmunizationwiththeotherantigens(P,0.05).Protectiveefficacywas measuredusing6-day-oldpupsrearedfromimmunizeddamsandorogastricallychallengedwithalethaldoseofElTorV. cholerae 01 Inaba strain N16961. Protection from death, and weight loss analysis at 24 and 48hours post-infection demonstratedthatimmunizationwithTcpFalonewaspoorlyprotective.However,immunizationwithTcpF+CTBwashighly protective and showed a trend toward greater protection than immunization with CTB alone (82% vs 64% survival). Immunization with the TcpF-A2-CTB chimera demonstrated less protection (50% survival) than immunization with the TcpF+CTBmixture.TheTcpF-A2-CTBchimerausedforthisstudycontainedtheheterologousclassicalCTBvariantwhereas theElTorCTBvariant(expressedbythechallengestrain)wasusedintheotherimmunizationgroups.Forallimmunization groups that received CTB, quantitative ELISA data demonstrated that the amounts of serum IgG directed against the homologousimmunizingCTBantigenwasstatisticallygreaterthantheamounttotheheterologousCTBantigen(P#0.003). ThisfindingprovidesalikelyexplanationforthepoorerprotectionobservedfollowingimmunizationwiththeTcpF-A2-CTB chimera and the relatively high level of protection seen after immunization with homologous CT