@article{ca7790bb70874cbf9fcecb68e15486dd,
title = "BCG vaccination provides protection against IAV but not SARS-CoV-2",
abstract = "Since the vast majority of species solely rely on innate immunity for host defense, it stands to reason that a critical evolutionary trait like immunological memory evolved in this primitive branch of our immune system. There is ample evidence that vaccines such as bacillus Calmette-Gu{\'e}rin (BCG) induce protective innate immune memory responses (trained immunity) against heterologous pathogens. Here we show that while BCG vaccination significantly reduces morbidity and mortality against influenza A virus (IAV), it fails to provide protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In contrast to IAV, SARS-CoV-2 infection leads to unique pulmonary vasculature damage facilitating viral dissemination to other organs, including the bone marrow (BM), a central site for BCG-mediated trained immunity. Finally, monocytes from BCG-vaccinated individuals mount an efficient cytokine response to IAV infection, while this response is minimal following SARS-CoV-2. Collectively, our data suggest that the protective capacity of BCG vaccination is contingent on viral pathogenesis and tissue tropism.",
keywords = "BCG vaccination, SARS-CoV-2, animal models, hematopoietic stem cells, influenza virus, lung pathology, monocytes, trained immunity",
author = "Eva Kaufmann and Nargis Khan and Tran, {Kim A.} and Antigona Ulndreaj and Erwan Pernet and Ghislaine Fontes and Andr{\'e}anne Lupien and Patrice Desmeules and Fiona McIntosh and Amina Abow and Moorlag, {Simone J.C.F.M.} and Priya Debisarun and Karen Mossman and Arinjay Banerjee and Danielle Karo-Atar and Mina Sadeghi and Samira Mubareka and Vinh, {Donald C.} and King, {Irah L.} and Robbins, {Clinton S.} and Behr, {Marcel A.} and Netea, {Mihai G.} and Philippe Joubert and Maziar Divangahi",
note = "Funding Information: The authors are grateful for the permission to use RNAscope images from a COVID-19 patient in this report. The authors acknowledge the support by the Histopathology Platforms at RI-MUHC, UHN Toronto, and IUCPQ Quebec City, as well as the support by the Animal Research Division at RI-MUHC. The authors thank Anisha Hundal for her assistance with ImageJ analysis for CD45 quantification. This work was supported by the Canadian Institutes of Health Research (CIHR) Project Grant (MM1-174910) to M.D. and I.L.K. as well as McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding awards to M.D. M.D. holds a Fonds de Recherche du Qu{\'e}bec - Sant{\'e} (FRQS) Award and the Strauss Chair in Respiratory Diseases. I.L.K. holds a Canada Research Chair in Barrier Immunity. C.S.R. holds a Peter Munk Chair in Aortic Disease Research. P.J. holds a FRQS Award. E.K. and N.K. were funded by postdoctoral Fellowships from FRQS and CIHR. A.U. is supported by a postdoctoral fellowship from the University of Toronto's Medicine by Design initiative. All models and the graphical abstract have been generated using BioRender. E.K. N.K. K.T. A.U. E.P. G.F. A.L. P.M. F.M. A.A. D.K.A. M.S. P.J. and M.D. performed experiments and analyzed data. S.J.C.F.M. P.D. K.M. A.B. and S.M. contributed cells, virus, reagents, and expertise. E.K. N.K. D.C.V. I.L.K. C.S.R. M.A.B. M.G.N. P.J. and M.D. designed experiments and discussed results and strategy. E.K. N.K. P.J. and M.D. wrote the manuscript. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. Funding Information: The authors are grateful for the permission to use RNAscope images from a COVID-19 patient in this report. The authors acknowledge the support by the Histopathology Platforms at RI-MUHC, UHN Toronto, and IUCPQ Quebec City, as well as the support by the Animal Research Division at RI-MUHC. The authors thank Anisha Hundal for her assistance with ImageJ analysis for CD45 quantification. This work was supported by the Canadian Institutes of Health Research (CIHR) Project Grant ( MM1-174910 ) to M.D. and I.L.K. as well as McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding awards to M.D. M.D. holds a Fonds de Recherche du Qu{\'e}bec - Sant{\'e} (FRQS) Award and the Strauss Chair in Respiratory Diseases. I.L.K. holds a Canada Research Chair in Barrier Immunity. C.S.R. holds a Peter Munk Chair in Aortic Disease Research. P.J. holds a FRQS Award. E.K. and N.K. were funded by postdoctoral Fellowships from FRQS and CIHR. A.U. is supported by a postdoctoral fellowship from the University of Toronto 's Medicine by Design initiative. All models and the graphical abstract have been generated using BioRender. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = mar,
day = "8",
doi = "https://doi.org/10.1016/j.celrep.2022.110502",
language = "American English",
volume = "38",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}
