Immunology of BCG vaccination in mice : implications for tuberculosis vaccination and for the use of BCG as a recombinant vaccine vector
Bibliographic record
Abstract
The effect of vaccination dose on the immune response of mice to Mycobacterium bovis Bacille Calmette-Guerin (BCG) was examined. To assess T helper cell-type 1 (Th1) and -type 2 (Th2) responses, a very sensitive ELISPOT assay was developed. Using this assay, the numbers of BCG-specific interferon ɣ- and interleukin 4-producing spleen cells were used as indicators of the Th1 and Th2 responses, respectively. IgG1 and IgG2a serum antibody titers were also assessed. Mice were immunized with different doses of BCG, and their immune response to BCG antigen was determined at various times after vaccination. Low dose immunized mice developed predominantly Th1 responses and little antibody, while those given higher numbers of bacilli generated a mixed Th1/Th2 response and had significant antibody titers. Furthermore, mice given the lower doses of BCG developed an immune imprint that enabled them to resist development of a Th2 response on subsequent challenge with a higher dose of BCG, which generates a Th2 response in previously unexposed mice. The immune response of mice immunized with recombinant BCG (rBCG) expressing 'Escherichia coli' β-galactosidase was also characterized. Th1 cells predominated in the immune response to BCG antigen as well as to the expressed β-galactosidase antigen in low dose vaccinated mice. Moreover, the Th1 response to both antigens was stable after high dose challenge of low dose vaccinated animals indicating that immune imprinting had been established both to BCG and to the recombinant β-galactosidase antigen. The results indicate that the immune state that develops in mice upon vaccination with BCG depends on the initial dose of antigen administered, with low amounts of antigen leading to Th1 immunity, and relatively high amounts of antigen leading to Th2 immune responses. 'Mycobacterium tuberculosis ' is only controlled effectively by a cell-mediated immune response. Immunization with a relatively low dose of BCG, rather than the current standard dose, may provide greater immune protection against 'M. tuberculosis'. Moreover, low dose vaccination with rBCG expressing proteins of leishmania or HIV promises to be an effective means of vaccination against diseases caused by these pathogens, which can only be contained by a Th1 response.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 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".