O16.2 Mapping regions of host attachment in the<i>T. pallidum</i>adhesin Tp0751: function-informed vaccine design
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".