Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study
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 inhibitio...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2022
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| _version_ | 1826307907929505792 |
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| author | Wilkie, M Tanner, R Wright, D Lopez Ramon, R Beglov, J Riste, M Marshall, JL Harris, SA Bettencourt, PJG Hamidi, A van Diemen, PM Moss, P Satti, I Wyllie, D McShane, H |
| author_facet | Wilkie, M Tanner, R Wright, D Lopez Ramon, R Beglov, J Riste, M Marshall, JL Harris, SA Bettencourt, PJG Hamidi, A van Diemen, PM Moss, P Satti, I Wyllie, D McShane, H |
| author_sort | Wilkie, M |
| collection | OXFORD |
| description | 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).
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| first_indexed | 2024-03-07T07:10:04Z |
| format | Journal article |
| id | oxford-uuid:f6b49498-ca87-4a3a-a8a1-b3de8bbfcfd8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:10:04Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:f6b49498-ca87-4a3a-a8a1-b3de8bbfcfd82022-06-10T07:07:49ZFunctional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6b49498-ca87-4a3a-a8a1-b3de8bbfcfd8EnglishSymplectic ElementsSpringer Nature2022Wilkie, MTanner, RWright, DLopez Ramon, RBeglov, JRiste, MMarshall, JLHarris, SABettencourt, PJGHamidi, Avan Diemen, PMMoss, PSatti, IWyllie, DMcShane, HBacille 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). |
| spellingShingle | Wilkie, M Tanner, R Wright, D Lopez Ramon, R Beglov, J Riste, M Marshall, JL Harris, SA Bettencourt, PJG Hamidi, A van Diemen, PM Moss, P Satti, I Wyllie, D McShane, H Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title | Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title_full | Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title_fullStr | Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title_full_unstemmed | Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title_short | Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study |
| title_sort | functional in vitro evaluation of the non specific effects of bcg vaccination in a randomised controlled clinical study |
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