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Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants

Abstract:

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-α2, TNF-α, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-022-34061-7

Authors

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Role:
Author
ORCID:
0000-0002-0823-5635
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Institution:
University of Oxford
Division:
MPLS
Department:
Biology
Role:
Author


Publisher:
Nature Research
Journal:
Nature Communications More from this journal
Volume:
13
Issue:
1
Article number:
6594
Publication date:
2022-11-03
Acceptance date:
2022-10-12
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
1300473
Local pid:
pubs:1300473
Deposit date:
2022-11-08
ARK identifier:

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