Mycobacterium bovis BCG substrains confer different levels of protection against Mycobacterium tuberculosis infection in a BALB/c model of progressive pulmonary tuberculosis

Abstract

Mycobacterium bovis BCG is the only available vaccine against tuberculosis. Reasons for why diverse BCG substrains induce different levels of protection in clinical trials remain unclear. The aim of this study was to compare the effectiveness of 10 BCG substrains in a mouse model of pulmonary tuberculosis. BALB/c mice were subcutaneously vaccinated and 2 months later were challenged with Mycobacterium tuberculosis H37Rv by intratracheal injection. Two and 4 months after challenge, delayed-type hypersensitivity (DTH) response, lung tissue affected by pneumonia, CFU, T-cell counts, and cytokine expression (interleukin-2 [IL-2], IL-4, IL-10, and gamma interferon) were determined. A differential protective effect of the diverse BCG substrains was found. BCG Phipps led to the largest and most persistent reduction of CFU counts and of the area of pneumonia at 2 and 4 months after challenge. This protection was accompanied by reduced IL-10-producing T cells. Contemporary BCG substrains induce a wide range of protection in this animal model. These data can help in the selection of the best vaccine for human immunization and for the development of novel recombinant BCG-based vaccine.

FIG. 1.

CD4⁺, CD8⁺ lymphocyte subset found in the lungs of mice immunized with 10 different BCG daughter strains 4 months after infection with Mycobacterium tuberculosis H37Rv. Analysis was performed on suspensions of pooled cells from four mice per group. Each bar represents the percentage of CD4⁺ and CD8⁺ T cells.

FIG. 2.

Local immune response in the lungs of mice immunized using BCG substrains and infected with Mycobacterium tuberculosis H37Rv. Nonvaccinated (control) and BCG-vaccinated groups were sacrificed 4 months after infection. Analysis was performed on suspensions of pooled cells from four mice per group. Data represent the percentage of cytokine-producing cells.