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

Iman Satti, Rachel E. Wittenberg, Shuailin Li, Stephanie A. Harris, Rachel Tanner, Deniz Cizmeci, Ashley Jacobs, Nicola Williams, Humphrey Mulenga, Helen A. Fletcher, Thomas J. Scriba, Michele Tameris, Mark Hatherill and Helen McShane ()
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Iman Satti: University of Oxford
Rachel E. Wittenberg: University of Oxford
Shuailin Li: University of Oxford
Stephanie A. Harris: University of Oxford
Rachel Tanner: University of Oxford
Deniz Cizmeci: University of Oxford
Ashley Jacobs: University of Oxford
Nicola Williams: University of Oxford, Radcliffe Observatory Quarter
Humphrey Mulenga: University of Cape Town
Helen A. Fletcher: London School of Hygiene & Tropical Medicine
Thomas J. Scriba: University of Cape Town
Michele Tameris: University of Cape Town
Mark Hatherill: University of Cape Town
Helen McShane: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-13

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

Date: 2022
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DOI: 10.1038/s41467-022-34061-7

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