Immunological Evidence for Functional Rather than Structural Mimicry by a<i>Shigella flexneri</i>Y Polysaccharide-Mimetic Peptide
Bibliographic record
Abstract
An approach to vaccine design is the use of molecules that mimic the immunogenic element of interest. In this context, the interaction of MDWNMHAA, a peptide mimic of the Shigella flexneri Y O polysaccharide (PS), with an anti-carbohydrate monoclonal antibody, as studied previously by X-ray crystallography, suggested the presence of functional rather than structural mimicry and a bound peptide conformation that was not represented significantly in the free-ligand ensemble. The antibody response elicited by an MDWNMHAA-carrier protein (tetanus toxoid [TT]) conjugate has now been investigated in BALB/c mice. The mice were immunized following a homologous prime/boost strategy using MDWNMHAA-TT as the immunogen. The mice showed anti-peptide antibody (immunoglobulin G [IgG]) titers that increased after being boosted. High anti-lipopolysaccharide (LPS) (IgG) titers were observed after the last boost. A faster immune response, with cross-reactive titers, was observed with a peptide conjugate with 30% more copies of the peptide. The binding of anti-peptide polyclonal antibodies to LPS could be inhibited by LPS, PS, MDWNMHAA, and MDWNMHAA-bovine serum albumin, as assessed by inhibition enzyme-linked immunosorbent assay. Conversely, mice immunized with PS-TT showed IgG anti-peptide titers. These data demonstrate the cross-reactivity of the antibody response and support the hypothesis that functional, as opposed to structural, mimicry of the S. flexneri Y O PS by MDWNMHAA or the underrepresentation of the bound ligand conformation in the free-ligand ensemble does not compromise immunological cross-reactivity. Prime/boost strategies were performed with a heterologous boost of PS-TT or MDWNMHAA-TT. They led to high anti-LPS titers after only three injections, suggesting alternatives to improve the immunogenicity of the carbohydrate-mimetic peptide and confirming the antigenic mimicry.
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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".