Vaccination with a low dose of BCG or BCG?BCG1419c protects against short-term Mycobacterium tuberculosis HN878 infection in male CB6F1 mice

Jorge Barrios-Payán, Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Cristian A. Segura-Cerda, Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, Biotecnología Médica y Farmacéutica, Jalisco, Guadalajara. Mexico
Dulce Mata-Espinosa, Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Helle Bielefeldt‑Ohmann, School of Chemistry and Molecular Biosciences, University of Queensland St. Lucia Campus, St Lucia, Austral
Rogelio Hernández-Pando, Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
Mario A. Flores-Valdez, Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, Biotecnología Médica y Farmacéutica, Jalisco, Guadalajara. Mexico

Introduction: Tuberculosis (TB) causes approximately 1.5 million deaths worldwide and 9 million new cases each year. Vaccination with Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is effective in controlling severe forms of TB in childhood, with limited efficacy in preventing lung disease in adults, which is further reduced by infection with Beijing strains. We previously showed that a standard human dose (105 colony-forming units [CFU]) of the BCGΔBCG1419c vaccine candidate delayed the progression of lung necrosis in male BALB/c mice infected with Mycobacterium tuberculosis (Mtb) HN878. Objective: To determine the protective efficacy of a low dose of 2 BCG strains against challenge with a hypervirulent strain of Mtb in a murine model. Material and methods: In this study, we explored the efficacy of vaccination with a low dose (102 CFUs) of BCG or BCGΔBCG1419c against Mtb HN878 infection in male CB6F1 mice, both at the short-term (1 month) and chronic (3 months post-infection) stages of active TB. Results: Vaccination with a low dose of BCG or BCGΔBCG1419c provided protection against Mtb HN878 challenge only 1 month after infection. Conclusion: Our results have important clinical translational implications, as they raise the hypothesis that the current vaccine may fail to protect humans against Beijing strains if, for example, problems occur during the handling, transportation, or administration of the current BCG vaccine (or a new one, such as BCGΔBCG1419c), leading to a lower than recommended dose being administered.

Keywords: Tuberculosis. Mycobacterium tuberculosis. Beijing. HN878. BCG. BCG?BCG1419c.