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Mycobacterium bovis BCG Substrains Confer Different Levels of Protection against Mycobacterium tuberculosis Infection in a BALB/c Model of Progressive Pulmonary Tuberculosis

Antonia Isabel Castillo-Rodal,^1, Mauricio Castañón-Arreola,^1, Rogelio Hernández-Pando,² Juan José Calva,² Eduardo Sada-Díaz,³ and Yolanda López-Vidal^1*

Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM),¹ Patología Experimental y Unidad de Epidemiología Clínica, Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán (INCMNSZ),² Servicio de Infectología, Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico³

Received 9 September 2005/ Returned for modification 9 October 2005/ Accepted 18 November 2005

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.

Editor: J. D. Clements

These authors contributed equally to the manuscript.

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