Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study

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dc.contributor.authorFletcher, Helen A
dc.contributor.authorFilali-Mouhim, Ali
dc.contributor.authorNemes, Elisa
dc.contributor.authorHawkridge, Anthony
dc.contributor.authorKeyser, Alana
dc.contributor.authorNjikan, Samuel
dc.contributor.authorHatherill, Mark
dc.contributor.authorScriba, Thomas J
dc.contributor.authorAbel, Brian
dc.contributor.authorKagina, Benjamin M
dc.contributor.authorVeldsman, Ashley
dc.contributor.authorAgudelo, Nancy Marín
dc.contributor.authorKaplan, Gilla
dc.contributor.authorHussey, Gregory D
dc.contributor.authorSekaly, Rafick-Pierre
dc.contributor.authorHanekom, Willem A
dc.date.accessioned2021-10-08T06:54:43Z
dc.date.available2021-10-08T06:54:43Z
dc.date.issued2016
dc.description.abstract: 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. : 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). : 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. : 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.
dc.identifier.apacitationFletcher, H. A., Filali-Mouhim, A., Nemes, E., Hawkridge, A., Keyser, A., Njikan, S., ... Hanekom, W. A. (2016). Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study. <i>BMC Medicine</i>, 14(1), 174 - 177. http://hdl.handle.net/11427/34319en_ZA
dc.identifier.chicagocitationFletcher, Helen A, Ali Filali-Mouhim, Elisa Nemes, Anthony Hawkridge, Alana Keyser, Samuel Njikan, Mark Hatherill, et al "Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study." <i>BMC Medicine</i> 14, 1. (2016): 174 - 177. http://hdl.handle.net/11427/34319en_ZA
dc.identifier.citationFletcher, H.A., Filali-Mouhim, A., Nemes, E., Hawkridge, A., Keyser, A., Njikan, S., Hatherill, M. & Scriba, T.J. et al. 2016. Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study. <i>BMC Medicine.</i> 14(1):174 - 177. http://hdl.handle.net/11427/34319en_ZA
dc.identifier.issn1741-7015
dc.identifier.ris TY - Journal Article AU - Fletcher, Helen A AU - Filali-Mouhim, Ali AU - Nemes, Elisa AU - Hawkridge, Anthony AU - Keyser, Alana AU - Njikan, Samuel AU - Hatherill, Mark AU - Scriba, Thomas J AU - Abel, Brian AU - Kagina, Benjamin M AU - Veldsman, Ashley AU - Agudelo, Nancy Marín AU - Kaplan, Gilla AU - Hussey, Gregory D AU - Sekaly, Rafick-Pierre AU - Hanekom, Willem A AB - : 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. : 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). : 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. : 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. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Medicine LK - https://open.uct.ac.za PY - 2016 SM - 1741-7015 T1 - Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study TI - Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study UR - http://hdl.handle.net/11427/34319 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34319
dc.identifier.vancouvercitationFletcher HA, Filali-Mouhim A, Nemes E, Hawkridge A, Keyser A, Njikan S, et al. Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study. BMC Medicine. 2016;14(1):174 - 177. http://hdl.handle.net/11427/34319.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Pathology
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Medicine
dc.source.journalissue1
dc.source.journalvolume14
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12916-016-0617-3
dc.subject.otherCorrelates of risk
dc.subject.otherSystems biology
dc.subject.otherTuberculosis
dc.subject.otherVaccine
dc.subject.otherAdjuvants, Immunologic
dc.subject.otherBCG Vaccine
dc.subject.otherCase-Control Studies
dc.subject.otherFemale
dc.subject.otherGene Expression Regulation, Bacterial
dc.subject.otherHumans
dc.subject.otherInfant
dc.subject.otherInfant, Newborn
dc.subject.otherMale
dc.subject.otherProspective Studies
dc.subject.otherTuberculosis
dc.subject.otherVaccination
dc.subject.otherAdjuvants, Immunologic
dc.titleHuman newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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