Divergent effect of bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: Implications for primate models in tuberculosis vaccine research

Despite the widespread use of bacillus Calmette-Guerin vaccination, Mycobac terium tuberculosis infection remains globally the leading cause of death f rom a single infectious disease. The complicated and often protracted dynam ics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promisin g candidates is therefore essential. Because macaque monkeys develop a dise ase very similar to humans, they have potential to provide important inform ation in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we comp ared the efficacy of bacillus Calmette-Guerin 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. t uberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette-Guerin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a stri king 2-log reduction in viable bacteria in the lungs compared with nonvacci nated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette-Guerin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lun gs. Comparative studies in these closely related species are likely to prov ide insight into mechanisms involved in protection against tuberculosis.