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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

Mucosal delivery of ESX-1-expressing BCG strains provides superior immunity against tuberculosis in murine type 2 diabetes.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 25 Aug 2020

Sathkumara HD, Muruganandah V, Cooper MM, Field MA, Alim MA, Brosch R, Ketheesan N, Govan B, Rush CM, Henning L, Kupz A,

Link to Pubmed [PMID] – 32778586

Link to DOI [DOI] – 10.1073/pnas.2003235117

Proc. Natl. Acad. Sci. U.S.A. 2020 Aug; 117(34): 20848-20859

Tuberculosis (TB) claims 1.5 million lives per year. This situation is largely due to the low efficacy of the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG) against pulmonary TB. The metabolic disease type 2 diabetes (T2D) is a risk factor for TB and the mechanisms underlying increased TB susceptibility in T2D are not well understood. Furthermore, it is unknown if new TB vaccines will provide protection in the context of T2D. Here we used a diet-induced murine model of T2D to investigate the underlying mechanisms of TB/T2D comorbidity and to evaluate the protective capacity of two experimental TB vaccines in comparison to conventional BCG. Our data reveal a distinct immune dysfunction that is associated with diminished recognition of mycobacterial antigens in T2D. More importantly, we provide compelling evidence that mucosal delivery of recombinant BCG strains expressing the Mycobacterium tuberculosis (Mtb) ESX-1 secretion system (BCG::RD1 and BCG::RD1 ESAT-6 ∆92-95) are safe and confer superior immunity against aerosol Mtb infection in the context of T2D. Our findings suggest that the remarkable anti-TB immunity by these recombinant BCG strains is achieved via augmenting the numbers and functional capacity of antigen presenting cells in the lungs of diabetic mice.

https://pubmed.ncbi.nlm.nih.gov/32778586