Isotype conversion of Staphylococcal-specific IgG into IgM broadens the reactivity to other bacterial pathogens
Bibliographic record
Abstract
Therapeutic antibodies are actively explored as alternative to treat or prevent bacterial infections. However, the narrow antigen specificity of IgG in combination with broad diversity in bacterial surface structures currently hampers the development of therapeutic antibodies against bacteria. Here we reveal that isotype conversion of three highly specific anti-staphylococcal antibodies from IgG into IgM does not only affect Fc effector functions but also modifies the interaction of Fab domains with bacterial surface antigens. These converted IgMs gain cross-reactivity for a broad range of bacterial species, including Gram-negatives such as Escherichia coli and Neisseria meningitidis and even protect against invasive infection with Streptococcus pyogenes in vivo. Mechanistic studies show that enhanced cross-specificity by IgM is conferred by changed ligand specificity and multivalent binding to high-density antigens. Altogether, these findings provide important insights for the development of antibody therapy for bacterial infections.
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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) | 0.002 | 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".