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Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
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Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
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Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
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Journal Article
Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
2022
Overview
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-
α
2, TNF-
α
, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with
M.tb
.
The identification of immune correlates of protection in humans would inform on the design and development of tuberculosis vaccine candidates. In this work, authors examine samples collected from South African infants, to determine whether the correlates of risk of tuberculosis disease, previously identified in this population, are also correlates of risk of M. tuberculosis infection.
