Construction and Characterization of the Mycobacterium tuberculosis sigE fadD26 Unmarked Double Mutant as a Vaccine Candidate

• Published in: Infection and immunity 2019-12, Vol.88 (1)
• Main Authors: Hernandez-Pando, Rogelio, Shin, Sung Jae, Clark, Simon, Casonato, Stefano, Becerril-Zambrano, Martin, Kim, Hongmin, Boldrin, Francesca, Mata-Espinoza, Dulce, Provvedi, Roberta, Arbues, Ainhoa, Marquina-Castillo, Brenda, Cioetto Mazzabò, Laura, Barrios-Payan, Jorge, Martin, Carlos, Cho, Sang-Nae, Williams, Ann, Manganelli, Riccardo
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins; Disease Models, Animal; Guinea Pigs; Ligases - deficiency; Mice; Microbial Immunity and Vaccines; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Sigma Factor - deficiency; Tuberculosis Vaccines - adverse effects; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Tuberculosis, Pulmonary - prevention & control; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Virulence
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00496-19

Despite the great increase in the understanding of the biology and pathogenesis of 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 ( 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 mutant of 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 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 mutant in different mouse models of infection and is equivalent to BCG in a guinea pig model of infection.