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


Fletcher, HA; Filali-Mouhim, A; Nemes, E; Hawkridge, A; Keyser, A; Njikan, S; Hatherill, M; Scriba, TJ; Abel, B; Kagina, BM; Veldsman, A; Agudelo, NM; Kaplan, G; Hussey, GD; Sekaly, RP; Hanekom, WA; BCG study team, ; , COLLABORATORS; Minnies, D; Tanner, R; Chung, CK; Cameron, MJ; Goulet, JP; Gaujoux, R; Hughes, J; Gelderbloem, S; Iloni, K; Buchanan, M; van der Merwe, L; Burger, A; Denation, L; Mlanjeni, S; Abrahams, S; Shepherd, R; Geldenhuys, M; Seoighe, C; Soares, A; Gamieldien, H; Sidibana, M; Mahomed, H; McShane, H; Hill, AV; (2016) Human newborn bacille Calmette-Guérin vaccination and risk of tuberculosis disease: a case-control study. BMC medicine, 14 (1). p. 76. ISSN 1741-7015 DOI: https://doi.org/10.1186/s12916-016-0617-3

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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.<br/> : 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).<br/> : 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.<br/> : 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: TB Centre
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PubMed ID: 27183822
Web of Science ID: 375907300001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2550473

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