Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosis sigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a Guinea pig model of infection.
Bibliographical noteFunding Information:
This work was supported by the European Community Seventh Framework Program (FP7/2007-2013) under grant agreement 241745 and by the Science and Technology Institute of Mexico City (grant agreement PICSA12-173). Experiments performed in the United Kingdom were supported by the Department of Health, United Kingdom. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
All Science Journal Classification (ASJC) codes
- Infectious Diseases