Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study
<p><strong>Background</strong></p> <p>An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease fol...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| מחברים אחרים: | |
| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
BioMed Central
2016
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| _version_ | 1826296538937163776 |
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| author | Fletcher, H Filali-Mouhim, A Nemes, E Hawkridge, A Keyser, A Njikan, S Hatherill, M Scriba, T Abel, B Kagina, B Veldsman, A Agudelo, N Kaplan, G Hussey, G Sekaly, R Hanekom, W BCG study team |
| author2 | McShane, H |
| author_facet | McShane, H Fletcher, H Filali-Mouhim, A Nemes, E Hawkridge, A Keyser, A Njikan, S Hatherill, M Scriba, T Abel, B Kagina, B Veldsman, A Agudelo, N Kaplan, G Hussey, G Sekaly, R Hanekom, W BCG study team |
| author_sort | Fletcher, H |
| collection | OXFORD |
| description | <p><strong>Background</strong></p> <p>An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette–Guérin (BCG) vaccination.</p> <p><strong>Methods</strong></p> <p>In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls).</p> <p><strong>Results</strong></p> <p>Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays.</p> <p><strong>Conclusions</strong></p> <p>Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.</p> |
| first_indexed | 2024-03-07T04:17:53Z |
| format | Journal article |
| id | oxford-uuid:ca024b02-1d1b-4e0b-a9d7-f935669fe3a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:17:53Z |
| publishDate | 2016 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:ca024b02-1d1b-4e0b-a9d7-f935669fe3a72022-03-27T07:04:19ZHuman newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ca024b02-1d1b-4e0b-a9d7-f935669fe3a7EnglishSymplectic Elements at OxfordBioMed Central2016Fletcher, HFilali-Mouhim, ANemes, EHawkridge, AKeyser, ANjikan, SHatherill, MScriba, TAbel, BKagina, BVeldsman, AAgudelo, NKaplan, GHussey, GSekaly, RHanekom, WBCG study teamMcShane, H<p><strong>Background</strong></p> <p>An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette–Guérin (BCG) vaccination.</p> <p><strong>Methods</strong></p> <p>In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls).</p> <p><strong>Results</strong></p> <p>Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays.</p> <p><strong>Conclusions</strong></p> <p>Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.</p> |
| spellingShingle | Fletcher, H Filali-Mouhim, A Nemes, E Hawkridge, A Keyser, A Njikan, S Hatherill, M Scriba, T Abel, B Kagina, B Veldsman, A Agudelo, N Kaplan, G Hussey, G Sekaly, R Hanekom, W BCG study team Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title | Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title_full | Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title_fullStr | Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title_full_unstemmed | Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title_short | Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study |
| title_sort | human newborn bacille calmette guerin vaccination and risk of tuberculosis disease a case control study |
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