Evaluation of the Protective Ability of the Treponema pallidum subsp. pallidum Tp0126 OmpW Homolog in the Rabbit Model of Syphilis.

In silico analyses of Treponema pallidum subsp. pallidum genomes and predicted proteomes to search for homologs of known bacterial outer membrane proteins (OMPs) led to the identification of tp0126 as a gene encoding a putative member of the OmpW family of porins/virulence factors. Our previous investigations on the role of Tp0126 in T. pallidum biology and syphilis pathogenesis showed that Tp0126 is fully conserved among T. pallidum strains and that transcription of tp0126 is driven by σ70 These initial results pointed to a housekeeping function for this protein. We also demonstrated that a guanosine homopolymer of various lengths located between the -10 and -35 consensus sequences in the tp0126 promoter modulates transcription consistently with phase variation, a mechanism that we also previously described for other T. pallidum genes encoding putative OMPs/virulence factors and that is often employed as a strategy for immune evasion. Circular dichroism spectra of recombinant Tp0126 also supported its structural homology with OmpW. Here we further investigated the humoral and cellular responses to Tp0126 during experimental and natural syphilis and the ability of Tp0126 to confer protection against syphilis in immunized rabbits. B-cell epitope mapping showed that compared to sera from experimentally infected animals, immunizations enhanced humoral immunity to sequences located in the putative Tp0126 surface-exposed loops, while phagocytosis assays showed that postimmunization sera opsonized T. pallidum Despite such promising results, no significant protection was seen following infectious challenge in immunized animals versus controls. Functional redundancy and phase variation might explain the lack of effectiveness of this vaccine candidate and/or design.