The innate inflammatory effects of the Gram-positive bacterium «Lactococcus lactis» and its application as live vaccines against leishmaniasis
Bibliographic record
Abstract
Lactococcus lactis is a non-pathogenic and non-colonizing Gram-positive bacterium commonly used in the dairy industry. Given its probiotic potential, the first objective of this thesis was to investigate the effects of L. lactis on the immune system. We compared the innate inflammatory effects of L. lactis with two Gram-negative bacterial strains: Escherichia coli, and attenuated Salmonella typhi, a widely used live bacterial vaccine. The gene expression profiles of chemokines induced by the three bacteria were examined in macrophages in vitro and in cells recruited into murine air-pouches in vivo. Also, we studied the effect of co-incubating bacteria with dendritic cells generated from mice bone marrow. We demonstrated that L. lactis may display inherent adjuvant activity since this bacterium exhibits innate inflammatory effects. These results support the use of L. lactis as a live bacterial vector to deliver biological molecules, such as vaccine antigens. The second objective of this thesis was to investigate the potential of using L. lactis to generate live vaccines against leishmaniasis. The parasite Leishmania affects a considerable number of individuals worldwide and is considered a neglected tropical disease by the World Health Organization. Although there are highly promising vaccine antigens and much ongoing research, there is still no vaccine available for clinical use against leishmaniasis. We engineered strains of L. lactis to express two known protective antigens against Leishmania: A2 and LACK. Both antigens were engineered for expression at differential subcellular localizations of L. lactis: in the cytoplasm, secreted into the media, or anchored to the cell-wall. Subcutaneous immunizations with live L. lactis vaccine strains were able to induce antigen-specific immune responses in mice. Moreover, we demonstrated that immunization with live L. lactis expressing A2 in the cytoplasm could protect mice against visceral Leishmania donovani infection,
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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".