Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate

Rogelio Hernandez-Pando, Sung Jae Shin, Simon Clark, Stefano Casonato, Martin Becerril-Zambrano, Hongmin Kim, Francesca Boldrin, Dulce Mata-Espinoza, Roberta Provvedi, Ainhoa Arbues, Brenda Marquina-Castillo, Laura Cioetto Mazzabò, Jorge Barrios-Payan, Carlos Martin, Sang Nae Cho, Ann Williams, Riccardo Manganelli

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Abstract

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.

Original languageEnglish
Article numbere00496-19
JournalInfection and Immunity
Volume88
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Hernandez-Pando, R., Shin, S. J., Clark, S., Casonato, S., Becerril-Zambrano, M., Kim, H., Boldrin, F., Mata-Espinoza, D., Provvedi, R., Arbues, A., Marquina-Castillo, B., Mazzabò, L. C., Barrios-Payan, J., Martin, C., Cho, S. N., Williams, A., & Manganelli, R. (2020). Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate. Infection and Immunity, 88(1), [e00496-19]. https://doi.org/10.1128/IAI.00496-19