Abstract |
Despite the widespread use of bacillus Calmette-Guérin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease very similar to humans, they have potential to provide important information in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we compared the efficacy of bacillus Calmette-Guérin vaccination and the course of infection in both species. Unvaccinated rhesus and cynomolgus monkeys both developed progressive disease with high levels of C-reactive protein, M. tuberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette-Guérin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a striking 2-log reduction in viable bacteria in the lungs compared with nonvaccinated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette-Guérin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lungs. Comparative studies in these closely related species are likely to provide insight into mechanisms involved in protection against tuberculosis.
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Authors | J A Langermans, P Andersen, D van Soolingen, R A Vervenne, P A Frost, T van der Laan, L A van Pinxteren, J van den Hombergh, S Kroon, I Peekel, S Florquin, A W Thomas |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 98
Issue 20
Pg. 11497-502
(Sep 25 2001)
ISSN: 0027-8424 [Print] United States |
PMID | 11562492
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Antibodies, Bacterial
- BCG Vaccine
- C-Reactive Protein
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Topics |
- Animals
- Antibodies, Bacterial
(blood, immunology)
- BCG Vaccine
(administration & dosage, immunology)
- C-Reactive Protein
(metabolism)
- Cells, Cultured
- Disease Models, Animal
- Drug Evaluation, Preclinical
(methods)
- Leukocytes, Mononuclear
(immunology)
- Macaca fascicularis
(immunology)
- Macaca mulatta
(immunology)
- Male
- Mycobacterium tuberculosis
(immunology)
- Species Specificity
- Tuberculosis
(immunology, pathology, prevention & control, veterinary)
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