Neonatal BCG vaccination reduces interferon gamma responsiveness to heterologous pathogens in infants from a randomised controlled trial



Freyne, Bridget ORCID: 0000-0002-9542-1582, Messina, Nicole, Germano, Susan, Bonnicci, Rhiain, Donath, Susan, Gardiner, Kaya, CAsalaz, Dan, Robins-Browne, Roy, Netea, Mihai, Flanagan, Katherine
et al (show 2 more authors) (2020) Neonatal BCG vaccination reduces interferon gamma responsiveness to heterologous pathogens in infants from a randomised controlled trial. Journal of Infectious Diseases.

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Abstract

Background Bacille Calmette-Guérin (BCG) vaccination has beneficial non-specific (heterologous) effects that protect against non-mycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial seven months after randomisation. Methods A whole blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands. Results Compared to BCG-naïve infants, BCG-vaccinated infants had increased production of MIG and IFN-γ in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation. Reduced IFN-γ responses to heterologous stimulants and TLR ligands were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG and IL-8, and decreased production of IL-10, MIP-1α and MIP-1ß, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination. Conclusions BCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation varies by pathogen.

Item Type: Article
Uncontrolled Keywords: Bacille Calmette-Guérin, Immunisation, Heterologous, Non-specific effects, Innate immunity, Infants
Depositing User: Symplectic Admin
Date Deposited: 17 Jan 2020 08:48
Last Modified: 07 Dec 2021 00:11
DOI: 10.1093/infdis/jiaa030
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3070969