• Patrice Akusa Mawa, Emily L Webb, Abdelali Filali-Mouhim, Gyaviira Nkurunungi, Rafick-Pierre Sekaly, Swaib Abubaker Lule, Sarah Prentice, Stephen Nash, Hazel M Dockrell, Alison M Elliott, and Stephen Cose.
• MRC/UVRI Uganda Research Unit on AIDS, P.O. Box 49, Entebbe, Uganda; London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Electronic address: pmawa@uvri.go.ug.
• Vaccine. 2017 Jan 5; 35 (2): 273-282.

IntroductionPrenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants.Material And MethodsMaternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other's effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray.ResultsMaternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus -0.94 in scar-negative, p=0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation.ConclusionsMaternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile.Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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