Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?
<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 infectio...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/8/1313 |
| _version_ | 1827728580135616512 |
|---|---|
| author | Sherridan Warner Anneliese Blaxland Claudio Counoupas Janine Verstraete Marco Zampoli Ben J. Marais Dominic A. Fitzgerald Paul D. Robinson James A. Triccas |
| author_facet | Sherridan Warner Anneliese Blaxland Claudio Counoupas Janine Verstraete Marco Zampoli Ben J. Marais Dominic A. Fitzgerald Paul D. Robinson James A. Triccas |
| author_sort | Sherridan Warner |
| collection | DOAJ |
| description | <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-Guérin (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. |
| first_indexed | 2024-03-10T23:32:01Z |
| format | Article |
| id | doaj.art-c57dfe974b3e40c3a066d698d5ebd63d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T23:32:01Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-c57dfe974b3e40c3a066d698d5ebd63d2023-11-19T03:17:20ZengMDPI AGVaccines2076-393X2023-08-01118131310.3390/vaccines11081313Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?Sherridan Warner0Anneliese Blaxland1Claudio Counoupas2Janine Verstraete3Marco Zampoli4Ben J. Marais5Dominic A. Fitzgerald6Paul D. Robinson7James A. Triccas8Sydney Infectious Diseases Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, AustraliaDepartment of Respiratory Medicine, The Children’s Hospital at Westmead, Westmead, NSW 2145, AustraliaSydney Infectious Diseases Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, AustraliaDepartment of Paediatrics and Child Health, Faculty of Health Science, University of Cape Town, Cape Town 7700, South AfricaDepartment of Paediatrics and Child Health, Faculty of Health Science, University of Cape Town, Cape Town 7700, South AfricaSydney Infectious Diseases Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, AustraliaDepartment of Respiratory Medicine, The Children’s Hospital at Westmead, Westmead, NSW 2145, AustraliaDepartment of Respiratory Medicine, The Children’s Hospital at Westmead, Westmead, NSW 2145, AustraliaSydney Infectious Diseases Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia<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-Guérin (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.https://www.mdpi.com/2076-393X/11/8/1313non-tuberculous mycobacteria<i>Mycobacterium abscessus</i>cystic fibrosisBCG vaccinationimmune response |
| spellingShingle | Sherridan Warner Anneliese Blaxland Claudio Counoupas Janine Verstraete Marco Zampoli Ben J. Marais Dominic A. Fitzgerald Paul D. Robinson James A. Triccas Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? Vaccines non-tuberculous mycobacteria <i>Mycobacterium abscessus</i> cystic fibrosis BCG vaccination immune response |
| title | Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? |
| title_full | Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? |
| title_fullStr | Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? |
| title_full_unstemmed | Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? |
| title_short | Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis? |
| title_sort | clinical and experimental determination of protection afforded by bcg vaccination against infection with non tuberculous mycobacteria a role in cystic fibrosis |
| topic | non-tuberculous mycobacteria <i>Mycobacterium abscessus</i> cystic fibrosis BCG vaccination immune response |
| url | https://www.mdpi.com/2076-393X/11/8/1313 |
| work_keys_str_mv | AT sherridanwarner clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT annelieseblaxland clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT claudiocounoupas clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT janineverstraete clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT marcozampoli clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT benjmarais clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT dominicafitzgerald clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT pauldrobinson clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis AT jamesatriccas clinicalandexperimentaldeterminationofprotectionaffordedbybcgvaccinationagainstinfectionwithnontuberculousmycobacteriaaroleincysticfibrosis |