AUTHOR=Lubyayi Lawrence , Mawa Patrice A. , Nabakooza Grace , Nakibuule Marjorie , Tushabe John Vianney , Serubanja Joel , Aibo Dorothy , Akurut Hellen , Tumusiime Josephine , Hasso-Agopsowicz Mateusz , Kaleebu Pontiano , Levin Jonathan , Dockrell Hazel M. , Smith Steven , Webb Emily L. , Elliott Alison M. , Cose Stephen 

TITLE=Maternal Latent Mycobacterium tuberculosis Does Not Affect the Infant Immune Response Following BCG at Birth: An Observational Longitudinal Study in Uganda

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00929

DOI=10.3389/fimmu.2020.00929

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> BCG has low efficacy in tropical countries. We hypothesized that maternal latent <italic>Mycobacterium tuberculosis (M.tb)</italic> infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization.</p><p><bold>Methods:</bold> We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. Cord blood and samples at weeks 1, 4, 6, 10, 14, 24, and 52 were analyzed for cytokine/chemokine responses to <italic>M.tb</italic> antigens by Luminex 17-plex assay in 6-day whole blood cultures and antibody responses by ELISA. Of the 17 Luminex analytes, seven (IL-2, IL-5, IL-10, IL-13, IL-17A, TNF, and IFN-γ) were included in the main analysis as they were considered most likely to represent T cell responses. Immune sensitization was defined as a detectable cord blood cytokine response to PPD for any of the seven cytokines. Patterns of cytokine and antibody responses were compared between infants of mothers with and without LTBI using linear mixed models adjusting for confounders.</p><p><bold>Results:</bold> Most infants (73%) were sensitized <italic>in utero</italic> to <italic>M.tb</italic> antigens, with no overall difference seen between infants born to mothers with or without LTBI. Patterns of post-BCG cytokine and antibody responses to mycobacterial antigens were similar between the two infant groups.</p><p><bold>Conclusions:</bold> Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.</p>