Seasonal variation in the non-specific effects of BCG vaccination on neonatal mortality: three randomised controlled trials in Guinea-Bissau

What is it about?

What is already known? • BCG vaccine non-specifically protects against other diseases than tuberculosis presumably via its immune-modulatory properties, training the innate immune system to enhanced response potential. • Malaria in pregnancy is associated with an immune-compromised phenotype in the newborn and a higher infant morbidity and mortality. What are the new findings? • Revisiting three randomized controlled trials of early BCG vaccination in low weight babies in Guinea-Bissau, we found that consistently over the course of the three trials spanning 12 years the protective effect of BCG on neonatal mortality was particularly observed when administered in November to January, with modest effects in the remaining months. • This seasonality was co-incident with the monthly malaria incidence pattern. • The immunological effects of BCG on pro-inflammatory adaptive and innate in vitro cytokine responses were stronger in the same months. What do the new findings imply? • We hypothesize that neonatal BCG vaccination ameliorates the detrimental immunological effects of malaria in pregnancy in the newborn, thereby increasing resilience against infectious insults in early life.

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