Parental Bacillus Calmette-Guérin vaccine scars decrease infant mortality in the first six weeks of life: A retrospective cohort study

Mlt Berendsen; F Schaltz-Buchholzer; P Bles; S Biering-Sørensen; K J Jensen; I Monteiro; I Silva; P Aaby; C S Benn

doi:10.1016/j.eclinm.2021.101049

Parental Bacillus Calmette-Guérin vaccine scars decrease infant mortality in the first six weeks of life: A retrospective cohort study

EClinicalMedicine. 2021 Aug 12:39:101049. doi: 10.1016/j.eclinm.2021.101049. eCollection 2021 Sep.

Authors

Mlt Berendsen^{1

2

3}, F Schaltz-Buchholzer^{1

2}, P Bles^{2

3}, S Biering-Sørensen², K J Jensen^{4

5}, I Monteiro², I Silva², P Aaby^{1

2}, C S Benn^{1

6}

Affiliations

¹ Bandim Health Project, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
² Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
³ Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kgs Lyngby, Denmark.
⁵ Center for Clinical Research and Prevention, Frederiksberg Hospital, Frederiksberg, Denmark.
⁶ Danish Institute for Advanced Study, University of Southern Denmark, Denmark.

Abstract

Background: Live attenuated vaccines have been observed to have particularly beneficial effects for child survival when given in the presence of maternally transferred immunity (priming). We aimed to test this finding and furthermore explore the role of paternal priming.

Methods: In an exploratory, retrospective cohort study in 2017, parental Bacillus Calmette-Guérin (BCG) scars were assessed for infants from the Bandim Health Project (BHP) who had participated in a 2008-2013 trial of neonatal BCG vaccination. Parental scar effects on mortality were estimated from birth to 42 days, the age of the scheduled diphtheria-tetanus-pertussis (DTP) vaccination, in Cox proportional hazard models adjusted with Inverse Probability of Treatment Weighting.

Findings: For 66% (510/772) of main trial infants that were still registered in the BHP area, at least one parent was located. BCG scar prevalence was 77% (353/461) among mothers and 63% (137/219) among fathers. In the first six weeks of life, maternal scars were associated with a mortality reduction of 60% (95%CI, 4% to 83%) and paternal scars with 49% (-68% to 84%). The maternal scar association was most beneficial among infants that had received BCG vaccination at birth (73% (-1% to 93%)). Although priming was less evident for paternal scars, having two parents with scars reduced mortality by 89% (13% to 99%) compared with either one or none of the parents having a scar.

Interpretation: Parental BCG scars were associated with strongly increased early-life survival. These findings underline the importance of future studies into the subject of inherited non-specific immunity and parental priming.

Funding: Danish National Research Foundation; European Research Council; Novo Nordisk Foundation; University of Southern Denmark.

Keywords: Bacille Calmette-Guérin; Heterologous effects; Immunological inheritance; Non-specific effects of vaccines; Parental priming; Vertical boosting.