Functional Characterization of Antibodies against Neisseria gonorrhoeae Opacity Protein Loops 英文参考文献.docVIP

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Functional Characterization of Antibodies against Neisseria gonorrhoeae Opacity Protein Loops 英文参考文献.doc

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Functional Characterization of Antibodies against Neisseria gonorrhoeae Opacity Protein Loops 英文参考文献

FunctionalCharacterizationofAntibodiesagainst NeisseriagonorrhoeaeOpacityProteinLoops JessicaG.Cole,AnnE.Jerse* DepartmentofMicrobiologyandImmunology,F.EdwardHe′bertSchoolofMedicine,UniformedServicesUniversityoftheHealthSciences,Bethesda,Maryland,United StatesofAmerica Abstract Background: The development of a gonorrhea vaccine is challenged by the lack of correlates of protection. The antigenically variable neisserial opacity (Opa) proteins are expressed during infection and have a semivariable (SV) and highlyconserved(4L)loopthatcouldbetargetedinavaccine.Herewecomparedantibodiestolinear(Ablinear)andcyclic (Abcyclic)peptidesthatcorrespondtotheSVand4Lloopsandselectedhypervariable(HV2)loopsforsurface-bindingand protectiveactivityinvitroandinvivo. Methods/Findings: AbSV cyclic bound a greater number of different Opa variants than AbSV linear, including variants that differedbysevenaminoacids.Antibodiestothe4LpeptidedidnotbindOpa-expressingbacteria.AbSV cyclicandAbHV2 cyclic , butnotAbSV linearorAbHV2 linearagglutinatedhomologousOpavariants,andAbHV2BD cyclicbutnotAbHV2BD linearblockedthe associationofOpaBvariantswithhumanendocervicalcells.OnlyAbHV2BD linearwerebactericidalagainsttheserumresistant parent strain. Consistent with host restrictions in the complement cascade, the bactericidal activity of AbHV2BD linear was increased8-foldwhenrabbitcomplementwasused.Noneoftheantibodieswasprotectivewhenadministeredvaginallyto mice. Antibody duration in the vagina was short-lived, however, with ,50% of the antibodies recovered 3hrs post- administration. Conclusions:WeconcludethatanSVloop-specificcyclicpeptidecanbeusedtoinduceantibodiesthatrecognizeabroad spectrum of antigenically distinct Opavariants and haveagglutination abilities. HV2 loop-specific cyclic peptides elicited antibodies with agglutination and adherence blocking abilities. The use of human complement when testing the bactericidalactivityofvaccine-inducedantibodiesagainstserumresistantgonoc