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AbstractTuberculosis 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-$$\alpha$$ α 2, TNF-$$\alpha$$ α , CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.

Original publication

DOI

10.1038/s41467-022-34061-7

Type

Journal article

Journal

Nature Communications

Publisher

Springer Science and Business Media LLC

Publication Date

03/11/2022

Volume

13