Evidence map›Paper›PMID 38621405›Full record

Trial reportThe Lancet. Infectious diseases2024

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.

Iman Satti, Julia L Marshall, Stephanie A Harris, Rachel Wittenberg, Rachel Tanner, Raquel Lopez Ramon, Morven Wilkie, Fernando Ramos Lopez, Michael Riste, Daniel Wright and 15 more

Open access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Experimental dissection of tuberculosis protective immunity: a human perspective.Frontiers in cellular and infection microbiology · 2025
    Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Vaccines · 2024
    Article
  20. bioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 3 institutions in 1 country.

Iman SattiThe Jenner Institute, University of Oxford, Oxford, UK.
Julia L MarshallThe Jenner Institute, University of Oxford, Oxford, UK.
Stephanie A HarrisThe Jenner Institute, University of Oxford, Oxford, UK.
Rachel WittenbergThe Jenner Institute, University of Oxford, Oxford, UK.
Rachel TannerThe Jenner Institute, University of Oxford, Oxford, UK.
Raquel Lopez RamonThe Jenner Institute, University of Oxford, Oxford, UK.
Morven WilkieThe Jenner Institute, University of Oxford, Oxford, UK.
Fernando Ramos LopezThe Jenner Institute, University of Oxford, Oxford, UK.
Michael RisteThe Jenner Institute, University of Oxford, Oxford, UK.
Daniel WrightThe Jenner Institute, University of Oxford, Oxford, UK.
Marco Polo Peralta AlvarezThe Jenner Institute, University of Oxford, Oxford, UK.
Nicola WilliamsNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Hazel MorrisonThe Jenner Institute, University of Oxford, Oxford, UK.
Elena StylianouThe Jenner Institute, University of Oxford, Oxford, UK.
Pedro FolegattiThe Jenner Institute, University of Oxford, Oxford, UK.
Daniel JenkinThe Jenner Institute, University of Oxford, Oxford, UK.
Samantha VermaakThe Jenner Institute, University of Oxford, Oxford, UK.
Linnea RaskThe Jenner Institute, University of Oxford, Oxford, UK.
Ingrid Cabrera PuigThe Jenner Institute, University of Oxford, Oxford, UK.
Rebecca Powell DohertyThe Jenner Institute, University of Oxford, Oxford, UK.
Alison LawrieThe Jenner Institute, University of Oxford, Oxford, UK.
Paul MossInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Timothy HinksOxford Centre for Respiratory Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Henry BettinsonOxford Centre for Respiratory Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Helen McShaneThe Jenner Institute, University of Oxford, Oxford, UK. Electronic address: helen.mcshane@ndm.ox.ac.uk.
University of Oxford · GBJenner Institute · GBUniversity of Birmingham · GB

Funding

Wellcome Trust 206331Wellcome Trust 211050
6 · The paper itself

Abstract

backgroundMycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG.

methodsThis phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 10

findingsParticipants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 10

interpretationThis first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection.

fundingBill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

Indexed as

BCG VaccineAdministration, InhalationAdolescentAdultAerosolsFemaleHumansInjections, IntradermalMaleMiddle AgedMycobacterium bovisTuberculosisUnited KingdomVaccines, AttenuatedYoung AdultAerosolsBCG VaccineVaccines, Attenuated

Identifiers

PMID38621405
PMCPMC7618001
OpenAlexW4394741599

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.