AUTHOR=Mawa Patrice A. , Hasso-Agopsowicz Mateusz , Lubyayi Lawrence , Nabakooza Grace , Nakibuule Marjorie , Blitz Rose , Dun Li , Govind Abha , Kaleebu Pontiano , Webb Emily L. , Elliott Alison M. , Dockrell Hazel M. , Cose Stephen , Smith Steven G. 

TITLE=Immune Responses Following BCG Immunization of Infants in Uganda and United Kingdom Are Similar for Purified Protein Derivative but Differ for Secretory Proteins of Mycobacterium tuberculosis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.637114

DOI=10.3389/fimmu.2021.637114

ISSN=1664-3224

ABSTRACT=<p><bold>Introduction:</bold> The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK.</p><p><bold>Materials and Methods:</bold> Blood samples were obtained from BCG-immunized infants of mothers with (<italic>n</italic> = 110) and without (<italic>n</italic> = 121) latent <italic>Mycobacterium tuberculosis</italic> infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (<italic>n</italic> = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with <italic>M. tuberculosis</italic> or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants.</p><p><bold>Results:</bold> The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1β, IL-1Ra, IP-10, MIP-1α, MIP-1β, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (<italic>p</italic> = 0.0001), IL-10 (<italic>p</italic> = 0.0022), and IL-13 (<italic>p</italic> = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52.</p><p><bold>Conclusions:</bold> Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.</p>