Salmonella Typhimurium expressing chromosomally integrated Schistosoma mansoni Cathepsin B protects against schistosomiasis in mice
Bibliographic record
Abstract
Abstract Schistosomiasis threatens hundreds of millions of people worldwide. The larval stage of Schistosoma mansoni migrates through the lung and adult worms reside adjacent to the colonic mucosa. Several candidate vaccines are in preclinical development, but none is designed to elicit both systemic and mucosal responses. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to express Cathepsin B (CatB), a digestive enzyme important for the juvenile and adult stages of the S. mansoni life cycle. Previous studies have demonstrated the prophylactic and therapeutic efficacy of our plasmid-based vaccine. Here, we have generated chromosomally integrated (CI) YS1646 strains that express CatB to produce a viable candidate vaccine for eventual human use (stability, no antibiotic resistance). 6–8-week-old C57BL/6 mice were vaccinated in a multimodal oral (PO) and intramuscular (IM) regimen, and then sacrificed 3 weeks later. The PO + IM group had significantly higher anti-CatB IgG titers with greater avidity and mounted significant intestinal anti-CatB IgA responses compared to PBS control mice (all P < 0.0001). Multimodal vaccination generated balanced TH1/TH2 humoral and cellular immune responses. Production of IFNγ by both CD4+ and CD8+ T cells was confirmed by flow cytometry (P < 0.0001 & P < 0.01). Multimodal vaccination reduced worm burden by 80.4%, hepatic egg counts by 75.2%, and intestinal egg burden by 78.4% (all P < 0.0001). A stable and safe vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with praziquantel mass treatment campaigns.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".