Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial
The Lancet Infectious Diseases·
- DOI
- 10.1016/s1473-3099(24)00143-9
- PMID
- 38621405
- PMCID
- PMC7618001
- OpenAlex
- W4394741599
- Study type
- Randomised controlled trial
- Publisher
- Elsevier BV
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The paper provides context for tuberculosis vaccine development by describing a controlled human infection model intended for future evaluation of vaccine efficacy and potential correlates of protection. It does not provide evidence about population-level tuberculosis surveillance or current disease activity.
Structured evidence summary
Research question
The study evaluated a safe aerosol dose of live-attenuated BCG for a controlled human infection model and compared its safety and tolerability with intradermal BCG administration.
Study design
This was a phase 1, randomised, controlled trial conducted at two UK clinical research facilities. It included aerosol BCG dose escalation followed by a randomised comparison of aerosol BCG with intradermal BCG, with safety as the primary outcome and BCG recovery as a secondary outcome.
Population and setting
Participants were healthy, immunocompetent adults aged 18-50 years in the UK who were naive to both M tuberculosis and BCG and had no asthma or other respiratory disease. The abstract reports 13 enrolled participants in the initial strain group and 33 in the subsequent strain group.
Main findings
Aerosol BCG doses up to 1 × 10^7 CFU were reported as sufficiently well tolerated. The frequency of systemic and respiratory adverse events did not differ significantly between aerosol and intradermal groups, although more severe systemic events occurred after aerosol BCG; all aerosol-associated adverse events resolved spontaneously. BCG was recovered from bronchoalveolar lavage after aerosol administration and from skin biopsies after intradermal administration.
Public-health relevance
The paper provides context for tuberculosis vaccine development by describing a controlled human infection model intended for future evaluation of vaccine efficacy and potential correlates of protection. It does not provide evidence about population-level tuberculosis surveillance or current disease activity.
Important limitations
The evidence comes from an early-phase study in a small, highly selected group of healthy UK adults, and the model uses attenuated BCG as a surrogate for M tuberculosis infection. The supplied material does not provide the full paper's detailed limitations; interpretation is therefore limited to the single-article abstract and metadata and requires the original paper for decision-grade assessment.
GIDS interpretation
The article is discoverable within tuberculosis, vaccination, and vaccine-effectiveness contexts because it evaluates a human infection model relevant to vaccine research. It should be treated as contextual research evidence only and does not confirm or characterize a live surveillance signal.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 10 auditable classifier relationships to diseases, places, topics, and study design.