Background Treponema pallidum ssp. pallidum (T. pallidum), the causative agent of syphilis, is a highly invasive pathogen that moves throughout the body via the bloodstream and invades every organ and tissue to cause the serious sequelae associated with sexually-transmitted and congenitally-acquired syphilis infections. Prevention of pathogen spread via the bloodstream is a critical requirement of a successful syphilis vaccine. The T. pallidum vaccine candidate Tp0751 is a host-binding adhesin that interacts with endothelial cells lining blood vessels. In this study we identify epitopes of Tp0751 that, when blocked with neutralizing monoclonal antibodies (mAbs), interrupt host endothelial cell interaction. This improved understanding will enhance antigen selection for syphilis vaccine development.

Methods Epitope localization of mAbs specific for Tp0751 was completed via enzyme-linked immunosorbent assays using several truncated versions of Tp0751. Following epitope localization, recombinant Tp0751 was incubated with individual mAbs and subsequently assayed for inhibition of Tp0751 adhesion to endothelial cells compared to that observed using control antibodies.

Results Epitope screening of Tp0751-specific mAbs identified functionally important regions of Tp0751 that mediate adherence to host cells. Inhibition studies revealed that all mAbs reactive against a defined C-terminal structural domain of Tp0751 impeded adherence of recombinant Tp0751 to endothelial cells. In contrast, N-terminal-reactive mAbs did not display this inhibition. These molecular studies allowed localization of neutralizing epitopes within a functionally important domain of the Tp0751 adhesin, which in turn assists with informed vaccine design.

Conclusion This study identified epitopes of Tp0751that are important for T. pallidum host cell adhesion. Host immune targeting of these functional regions may facilitate antibody-dependent neutralization of treponemal dissemination, which is needed to establish protective immunity against T. pallidum. These results further our understanding of T. pallidum host cell adhesion and allow refinement of antigen selection for syphilis vaccine development.

Disclosure No significant relationships.