The effect of BCG vaccination on systemic inflammation in neonates

Vaccine: Volume 75, Page 128241

OBJECTIVES: To assess the impact of BCG vaccination on systemic inflammation in neonates, focusing on sex-specific differences and the relationship between circulating inflammatory proteins and immune responses, including cytokine production and antibody levels. METHODS: A randomized clinical trial was conducted in Denmark involving newborns who were randomized to receive BCG vaccine or not. Blood samples were collected at 4 days, 3 months and 13 months post-randomization. In the current sub-study within the randomized clinical trial, ninety-two inflammatory proteins in plasma were measured using a proximity extension assay. We analysed the changes in these inflammatory markers and examined their association with immune markers. RESULTS: Before BCG vaccination, girls had slightly higher inflammatory marker levels than boys. Post-vaccination, a moderate decrease in circulating inflammatory markers was noted in BCG-vaccinated children, especially in girls, with the strongest effects observed at 3 months. By 13 months, following routine vaccinations, there was no longer any measurable effect of BCG vaccination. BCG seemed to modify the associations between inflammatory proteins and immune responses. CONCLUSIONS: This sub-study suggests that BCG vaccination could temporally reduce systemic inflammation in neonates, with the strongest effect observed in girls, who had the highest baseline levels. These findings seemingly replicate observations in adults, showing that BCG has a pronounced inflammation-dampening effect in those with higher pre-vaccination levels. The results further show that BCG vaccination could alter circulating inflammatory proteins in a time-dependent manner and potentially modulate the associations between inflammatory markers and immune function. These insights highlight the importance of sex-specific immune modulation by BCG in early life and underscore the value of personalised vaccination strategies that considers both timing and sex differences in immune responses.

DOI: 10.1016/j.vaccine.2026.128241