A second-generation recombinant BCG strain combines protection against murine tuberculosis with an enhanced safety profile in immunocompromised hosts

Vaccine. 2024 Oct 24;42(24):126291. doi: 10.1016/j.vaccine.2024.126291. Epub 2024 Sep 5.

Abstract

Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.

Keywords: Immunocompromised mice; Recombinant BCG; Tuberculosis; Vaccine development.

MeSH terms

  • Animals
  • BCG Vaccine* / adverse effects
  • BCG Vaccine* / genetics
  • BCG Vaccine* / immunology
  • Disease Models, Animal
  • Female
  • Immunocompromised Host*
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / immunology
  • Mycobacterium bovis / pathogenicity
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control
  • Vaccine Efficacy
  • Vaccines, Synthetic* / administration & dosage
  • Vaccines, Synthetic* / adverse effects
  • Vaccines, Synthetic* / genetics
  • Vaccines, Synthetic* / immunology

Substances

  • BCG Vaccine
  • Vaccines, Synthetic