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Open Access 01-12-2016 | Research article

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

Authors: Helen A. Fletcher, Ali Filali-Mouhim, Elisa Nemes, Anthony Hawkridge, Alana Keyser, Samuel Njikan, Mark Hatherill, Thomas J. Scriba, Brian Abel, Benjamin M. Kagina, Ashley Veldsman, Nancy Marín Agudelo, Gilla Kaplan, Gregory D. Hussey, Rafick-Pierre Sekaly, Willem A. Hanekom, the BCG study team

Published in: BMC Medicine | Issue 1/2016

Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

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Title: Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study
Authors: Helen A. Fletcher
Ali Filali-Mouhim
Elisa Nemes
Anthony Hawkridge
Alana Keyser
Samuel Njikan
Mark Hatherill
Thomas J. Scriba
Brian Abel
Benjamin M. Kagina
Ashley Veldsman
Nancy Marín Agudelo
Gilla Kaplan
Gregory D. Hussey
Rafick-Pierre Sekaly
Willem A. Hanekom
the BCG study team
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2016
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-016-0617-3

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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