Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?

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dc.contributor.authorWarner, Sherridan
dc.contributor.authorBlaxland, Anneliese
dc.contributor.authorCounoupas, Claudio
dc.contributor.authorVerstraete, Janine
dc.contributor.authorZampoli, Marco
dc.contributor.authorMarais, Ben J.
dc.contributor.authorFitzgerald, Dominic A.
dc.contributor.authorRobinson, Paul D.
dc.contributor.authorTriccas, James A.
dc.date.accessioned2023-09-15T10:44:22Z
dc.date.available2023-09-15T10:44:22Z
dc.date.issued2023-08-01
dc.date.updated2023-08-25T12:37:09Z
dc.description.abstractMycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD up sup T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.
dc.identifierdoi: 10.3390/vaccines11081313
dc.identifier.apacitationWarner, S., Blaxland, A., Counoupas, C., Verstraete, J., Zampoli, M., Marais, Ben J., ... Triccas, James A. (2023). Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?. <i>Vaccines</i>, 11(8), 1313. http://hdl.handle.net/11427/38694en_ZA
dc.identifier.chicagocitationWarner, Sherridan, Anneliese Blaxland, Claudio Counoupas, Janine Verstraete, Marco Zampoli, Ben J. Marais, Dominic A. Fitzgerald, Paul D. Robinson, and James A. Triccas "Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?." <i>Vaccines</i> 11, 8. (2023): 1313. http://hdl.handle.net/11427/38694en_ZA
dc.identifier.citationWarner, S., Blaxland, A., Counoupas, C., Verstraete, J., Zampoli, M., Marais, Ben J., Fitzgerald, Dominic A. & Robinson, Paul D. et al. 2023. Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?. <i>Vaccines.</i> 11(8):1313. http://hdl.handle.net/11427/38694en_ZA
dc.identifier.risTY - Journal Article AU - Warner, Sherridan AU - Blaxland, Anneliese AU - Counoupas, Claudio AU - Verstraete, Janine AU - Zampoli, Marco AU - Marais, Ben J. AU - Fitzgerald, Dominic A. AU - Robinson, Paul D. AU - Triccas, James A. AB - <i>Mycobacterium abscessus</i> is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Gu&eacute;rin (BCG) vaccination may impact NTM infection, using a murine model of <i>Mycobacterium abscessus</i> infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4<sup>+</sup> T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with <i>M. abscessus</i> afforded the highest level of protection against <i>M. abscessus</i> challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4<sup>+</sup> T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for <i>M. abscessus</i>. This study provides evidence that routine BCG vaccination may reduce <i>M. abscessus</i> colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4<sup>+</sup> T cells recognising <i>M. abscessus</i> in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF. DA - 2023-08-01 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PY - 2023 T1 - Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? TI - Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? UR - http://hdl.handle.net/11427/38694 ER -en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/38694
dc.identifier.vancouvercitationWarner S, Blaxland A, Counoupas C, Verstraete J, Zampoli M, Marais Ben J, et al. Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?. Vaccines. 2023;11(8):1313. http://hdl.handle.net/11427/38694.en_ZA
dc.publisherMultidisciplinary Digital Publishing Institute
dc.publisher.departmentPaediatrics and Child Health
dc.publisher.facultyHealth Science
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceVaccines
dc.source.journalissue8
dc.source.journalvolume11
dc.source.pagination1313
dc.source.urihttps://www.mdpi.com/journal/vaccines
dc.titleClinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?
dc.typeJournal Article
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