Generation and evaluation of SMT-expressing «Lactococcus lactis» live vaccines against visceral leishmaniasis
Bibliographic record
Abstract
Lactococcus lactis is a Gram-positive lactic acid bacterium commonly used in the dairy industry. It has been deemed safe for human consumption by the United States Food and Drug Administration and holds Generally Recognised As Safe (GRAS) status. L. lactis is non-pathogenic, non-colonizing and non-invasive. The utility of this bacterium as a cell "factory" able to synthesis heterologous proteins is now well established. Previous work in our lab has also shown that L. lactis has the ability to stimulate the innate immune system. All these properties make L. lactis a suitable vector for biological delivery of antigens to stimulate an immune response.Visceral leishmaniasis is a disseminated protozoan infection, caused by the species of the Leishmania donovani complex, which affects the liver, spleen and bone marrow. There are 500,000 new cases of visceral leishmaniasis every year and 90% of clinical cases are fatal if left untreated. In addition to the disadvantages of high cost and side effects of chemotherapy, there is also emerging resistance of parasites to anti-leishmanial drugs. In light of these facts, the development of a vaccine against visceral leishmaniasis is a priority. We have engineered L. lactis (strains NZ9000 and PH3960) to heterologously express the protective Leishmania antigen, sterol 24-c-methyltransferase (SMT), in the cytoplasm. In separate studies, these strains of L. lactis were assessed for their protective capability as live vaccines against L. donovani in BALB/c mice, both individually and adjuvanted with IL-12-secreting L. lactis. Immune responses to subcutaneous immunizations were monitored by measuring serum antibody titers against SMT and cytokine production from splenocytes upon stimulation by soluble Leishmania antigen at the end point of infection. Mice immunised with SMT-expressing clones of L. lactis NZ9000 had high titers of both serum IgG1 and IgG2a as well as splenocyte cytokine response profiles which demonstrated a mixed Th1/Th2 response. The co-administration of SMT- and murine IL-12-producing L. lactis clones was able to reduce parasite load in the liver significantly in the case of L. lactis NZ9000. Overall, we demonstrated that L. lactis is a suitable vehicle for the delivery of vaccine antigens and generation of protective immune responses against visceral leishmaniasis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".