Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG.

Summary

In a blinded randomized aerosol challenge of BCG-naïve adults, investigators characterized the earliest airway mucosal immune responses to inhaled BCG and explored correlates of in vitro protection. The model provides a controlled human platform to dissect mucosal immunity relevant to tuberculosis vaccines.

Key Findings

• A blinded randomized aerosol human challenge with attenuated BCG characterized early airway mucosal immune responses.
• The study prospectively identified immune markers associated with in vitro protection after inhaled BCG.
• Demonstrated feasibility of controlled aerosol infection to study human mucosal immunity relevant to tuberculosis.

Clinical Implications

While not practice-changing yet, the work informs selection of mucosal endpoints and biomarkers for next-generation TB vaccines and suggests feasibility and safety parameters for aerosolized vaccine evaluation.

Limitations

• Attenuated BCG is a surrogate for M. tuberculosis and may not fully recapitulate pathogenic responses
• Likely small sample size and short follow-up focused on early responses

Future Directions

Validate identified mucosal biomarkers as correlates of protection in vaccine trials, expand to diverse populations, and compare aerosolized vaccine candidates using standardized endpoints.