Scientific Reports (May 2022)

Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study

  • Morven Wilkie,
  • Rachel Tanner,
  • Daniel Wright,
  • Raquel Lopez Ramon,
  • Julia Beglov,
  • Michael Riste,
  • Julia L. Marshall,
  • Stephanie A. Harris,
  • Paulo J. G. Bettencourt,
  • Ali Hamidi,
  • Pauline M. van Diemen,
  • Paul Moss,
  • Iman Satti,
  • David Wyllie,
  • Helen McShane

DOI
https://doi.org/10.1038/s41598-022-11748-x
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 13

Abstract

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Abstract Bacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from four bacteria implicated in infant mortality. Volunteers were randomised to receive BCG intradermally (n = 27) or to be unvaccinated (n = 8) and were followed up for 84 days; laboratory staff were blinded until completion of the final visit. Using GIAs based on peripheral blood mononuclear cells, we observed a significant reduction in the growth of the Gram-negative bacteria Escherichia coli and Klebsiella pneumonia following BCG vaccination, but no effect for the Gram-positive bacteria Staphylococcus aureus and Streptococcus agalactiae. There was a modest association between S. aureus nasal carriage and growth of S. aureus in the GIA. Our findings support a causal link between BCG vaccination and improved ability to control growth of heterologous bacteria. Unbiased assays such as GIAs are potentially useful tools for the assessment of non-specific as well as specific effects of TB vaccines. This study was funded by the Bill and Melinda Gates Foundation and registered with ClinicalTrials.gov (NCT02380508, 05/03/2015; completed).