BCG vaccination–induced emergency granulopoiesis provides rapid protection from neonatal sepsis

Byron Brook(University of British Columbia), Danny Harbeson(University of British Columbia), Casey P. Shannon(St. Paul's Hospital), Bing Cai(BC Children's Hospital), Daniel He(University of British Columbia), Rym Ben-Othman(BC Children's Hospital), Freddy Francis(University of British Columbia), Yue Z. Huang(BC Children's Hospital), Natallia Varankovich(BC Children's Hospital), Aaron C. Liu(University of British Columbia), Winnie Bao(BC Children's Hospital), Morten Bjerregaard-Andersen(Statens Serum Institut), Frederik Schaltz‐Buchholzer(Statens Serum Institut), Lilica Sanca(Bandim Health Project), Christian N Golding(Statens Serum Institut), Kristina Lindberg Larsen(Statens Serum Institut), Ofer Levy(Broad Institute), Beate Kampmann(University of London), Rusung Tan(Weill Cornell Medical College in Qatar), Adrian Charles(Weill Cornell Medical College in Qatar), James L. Wynn(University of Florida), Frank Shann(The University of Melbourne), Peter Aaby(Bandim Health Project), Christine Stabell Benn(Statens Serum Institut), Scott J. Tebbutt(University of British Columbia), Tobias R. Kollmann(University of British Columbia), Nelly Amenyogbe(University of British Columbia), Amy Huei‐Yi Lee, Tue Bjerg Bennike, Joann Diray‐Arce, Olubukola T. Idoko, William Pomat, Simon D. van Haren, Momoudou Cox, Alansana Darboe, Reza Falsafi, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Arnaud Marchant, Peter Richmond, Rebecca Ford, G Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzman Sánchez‐Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Ryan R. Brinkman, Al Ozonoff(Statens Serum Institut), Robert E. W. Hancock, Anita H.J. van den Biggelaar, Hanno Steen(St. Paul's Hospital), Diana Vo, Ken Kraft, Kerry McEnaney, Sofia M. Vignolo
Science Translational Medicine
May 6, 2020
10.1126/scitranslmed.aax4517
Cited by 127Open Access
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Abstract

Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient to drive emergency granulopoiesis (EG), resulting in a marked increase in neutrophils. This increase in neutrophils was directly and quantitatively responsible for protection from sepsis. Rapid induction of EG after BCG administration also occurred in three independent cohorts of human neonates.

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