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, 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
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).
Conflict of interest statement
The authors declare no competing interests.
© 2022. The Author(s).
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References
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