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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Medicine 1/2016

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

Zeitschrift:
BMC Medicine > Ausgabe 1/2016
Autoren:
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
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Electronic supplementary material

The online version of this article (doi:10.​1186/​s12916-016-0617-3) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

AH, AK, MH, AV, GK, GDH and WAH were involved in clinical design and execution, including blood collection and storage. HAF, AF-M, EN, AK, SN, BA, BJM, GK, R-PS and WAH were involved in design and execution of blood analysis. HAF, AF-M, EN, R-PS and WAH wrote the manuscript, with input from all other authors. WAH was the principal investigator of the project. TJS and NMA were also involved in design and execution of blood analysis. All authors read and approved the final manuscript.

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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