ArticlePLoS pathogens2026
Improved immune responses and tuberculosis protection by aerosol vaccination with recombinant BCG expressing ESX-1 from Mycobacterium marinum.
Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Genetically diverse CC and DO mouse models enable comprehensive assessments of novel tuberculosis vaccines.NPJ vaccines · 2026Article
- An ESAT-6-convergent prime-boost vaccination combining recombinant BCG expressing Mycobacterium marinum ESX-1 and ESAT-6/GLA-SE improves TB protection.NPJ vaccines · 2026Article
- Clinical characteristics, drug resistance profiles, and inflammatory cytokine signatures in newly treated versus retreated MDR/RR-TB patients: associations with treatment outcomes.Frontiers in microbiology · 2026Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The currently licensed anti-tuberculosis (TB) vaccine, Mycobacterium bovis BCG, provides limited protection against pulmonary TB in adolescents and adults, the main cause of TB transmission and mortality. To obtain an improved BCG-based vaccine candidate with increased immune signalling but still low virulence, we have previously generated a recombinant BCG strain named BCG::ESX-1Mmar, which is heterologously expressing ESX-1 functions of Mycobacterium marinum and thereby modulates the host innate immune responses via phagosomal rupture-associated induction of type I interferon production and enhanced inflammasome activity, leading to superior protection against TB disease in murine infection models. As protection may also vary with the route of vaccination, here, we have explored aerosol vaccination relative to subcutaneous vaccination, using BCG Pasteur and BCG::ESX-1Mmar. We found that mice vaccinated via the aerosol route with BCG Pasteur or BCG::ESX-1Mmar both yielded higher frequencies of CD4+ and CD8+ Th1 activated effectors and T effector memory cells in the lungs compared to subcutaneously immunised mice, whereas comparable polyfunctional Th1 (IL-2, TNF-α and IFN-γ) cytokine-producing subsets were observed in the spleens of all vaccinated mice. Significantly higher IL-17A responses without severe lung pathology were seen in the lungs of aerosol-vaccinated mice associated to local and transient inflammatory cytokine responses and immune cell infiltrations. In contrast to the subcutaneous route, aerosol vaccination elicited high amounts of humoral IgG and IgA responses in the bronchoalveolar lavage fluid and induced a substantial number of lung CD4+ and CD8+ T cells expressing CD69+ CD103+ tissue-residency markers. These effects led to significant improved protection against M. tuberculosis and reduced lung pathology in aerosol-vaccinated mice compared to subcutaneously vaccinated mice. Moreover, BCG::ESX-1Mmar vaccine induced enhanced T-cell immunity and superior protection compared to parental BCG Pasteur for both vaccination routes and thereby represents an interesting candidate for developing improved vaccination strategies against TB.
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