Maternal BCG primes for enhanced health benefits in the newborn

Abstract

Objectives: Bacille Calmette-Guérin (BCG) vaccination lowers the risk of severe infection; we tested whether effects are modulated by maternal BCG in a large cohort of BCG-vaccinated newborns from Guinea-Bissau.

Methods: Maternal BCG scar status were inspected at enrolment in a BCG trial conducted from 2014 to 17 in Bissau, Guinea-Bissau. We tested associations with background factors for potential confounding; maternal age affected effect estimates >5% and accordingly, all analyses were adjusted for maternal age. Hospitalization data was collected prospectively and assessed in Cox-models providing adjusted Incidence Rate Ratios (aIRRs). In-hospital risk of death (case-fatality) risk was assessed using binomial regression providing adjusted Risk Ratios (aRRs).

Results: 60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81-1.14) from 0 to 6 weeks and 1.12 (0.97-1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34-1.05); 0.40 (0.17-0.91) for males and 0.86 (0.38-1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26-0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates.

Conclusion: Among BCG-vaccinated newborns, there was a trend for fewer in-hospital deaths from infection associated with maternal BCG priming, especially for males. Providing BCG to adults without a vaccination scar might enhance their offspring's capacity to handle severe infections. Brief 40-word summary: Within a trial comparing BCG strains for their overall effects on morbidity and mortality in Guinea-Bissau, vertical priming with BCG (represented by the maternal BCG scar) was associated with beneficial sex-differential effects on offspring survival.

Trial registration: ClinicalTrials.gov NCT02447536.

Keywords: Bacille Calmette-Guérin (BCG); Early-life morbidity and mortality; Live-vaccines; Maternal BCG priming; Non-specific effects of vaccines; Vertical priming.

Conflict of interest statement

Declaration of Competing Interest At the time the data collection was conducted, several of the authors were affiliated with the Statens Serum Institute (SSI) in Copenhagen which administered, but did not finance, their grants. SSI was a producer of BCG. However, SSI did not fund the vaccines, the study, or the researchers and neither the SSI or funders had any influence on the study design, data collection, analysis, interpretation or writing of the report, nor the decision to submit the paper for publication. None of the authors have any commercial, financial, or personal interests, relationships or other associations that might pose a conflict of interest in relation to this study. Data sharing agreement. Deidentified participant data with a data dictionary can be shared after approval of a data-sharing proposal sent to Professor Christine Stabell Benn (cbenn@health.sdu.dk).

Copyright © 2021. Published by Elsevier Ltd.