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

Research output: Contribution to journalArticlepeer-review

Abstract

Bacille Calmette-Guerin (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).
Original languageEnglish
Article number7808
Number of pages13
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 12 May 2022

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