(L-R) Maziar Divangahi, PhD, Eva Kaufmann, PhD, Kim Tran, Nargis Khan, PhD, Erwan Pernet, PhD (Photo by Alexandre Grant).

A new study led by RI-MUHC researchers reveals that the 100-year-old tuberculosis vaccine known as BCG can provide protection against respiratory infections like influenza, but not against SARS-CoV-2.

Recently published in Cell Reports, researchers from the Research Institute of the McGill University Health Centre (RI-MUHC) worked with national and international collaborators to study the effect of the Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2, the virus that causes COVID-19. BCG is well known to be safe and effective against a wide range of viral infections including influenza, but its effect on SARS-CoV-2 was unknown.

“The BCG vaccine has a remarkable track record,” says Maziar Divangahi, PhD, scientist in the Translational Research in Respiratory Diseases Program (RESP) at the RI-MUHC and lead author on the study. “In the early days of the COVID-19 pandemic, epidemiological studies suggested that national BCG vaccination programs were associated with reduced COVID-19 morbidity and mortality across borders and age groups. This led to several large-scale BCG clinical trials around the world.”

The RI-MUHC team collaborated with Laval University, McMaster University, University of Toronto, and Radboud University in the Netherlands. The goal of their joint work was to address the question of whether the BCG vaccine would enhance immunogenicity and protection against SARS-CoV-2, using both clinical and preclinical approaches.

“Prior to our study, we were quite confident that BCG would provide protection against SARS-CoV-2,” says Kim Tran, PhD candidate and co-author. “This is because our data showed that BCG vaccination provided a remarkable protection against H1N1.”

“When we found that BCG vaccination in murine models of COVID-19 did not provide protection against SARS-CoV-2, we were very surprised,” says Eva Kaufmann, PhD, first author of the study and a postdoctoral fellow in the Divangahi lab. “We initially thought our finding might be due to the mouse model that does not naturally express the ACE2 receptor, which is required for entry of SARS-CoV-2 into the host cells.”

“We therefore decided to use two hamster models, as they naturally express ACE2 receptor and can represent the moderate and severe forms of COVID-19,” she adds. “Again, we found that BCG did not provide protection.”

“Additionally, by evaluating the pathology of the lung, we found that the extent of tissue damage and pulmonary hemorrhage was profound with SARS-CoV-2 compared to H1N1,” says Philippe Joubert, MD, PhD, a pulmonary pathologist at Université Laval and also a corresponding author on this study. “SARS-CoV-2, but not H1N1, has the capacity to infect endothelial cells that line the lung vasculature and express the ACE2 receptor. This might be the major difference between these two respiratory viruses.”

“It’s interesting that we then found SARS-CoV-2 viral RNA in bone marrow,” says Nargis Khan, PhD, also a postdoctoral fellow in the Divangahi lab and co-first author of this study. “Bone marrow holds stem cells that generate the many cell types of the blood, including those that can provide immunity against pathogenic respiratory viruses. Many protective effects of BCG have been attributed to these stem cells. If a pathogen gets access into the bone marrow, it may erase this protection. We are now testing this hypothesis.”

“Despite the fact that BCG has been around for a century, our understanding of its protective mechanisms against TB and other infectious diseases is still extremely limited,” concludes Maziar Divangahi. “Although BCG does not seem to provide cross-protection against SARS-CoV-2, future research is needed to show if it could instead enhance immune responses to SARS-CoV-2-specific vaccines, or help overcome the short-lived efficacy of the currently available mRNA vaccines against COVID-19.”

About the study:

The study “BCG vaccination provides protection against IAV but not SARS-CoV-2” was conducted by Eva Kaufmann, Nargis Khan, Kim A. Tran, Antigona Ulndreaj, Erwan Pernet, Ghislaine Fontes, Andréanne Lupien, Patrice Desmeules, Fiona McIntosh, Amina Abow, Simone J.C.F.M. Moorlag, Priya Debisarun, Karen Mossman, Arinjay Banerjee, Danielle Karo-Atar, Mina Sadeghi, Samira Mubareka, Donald C. Vinh, Irah L. King, Clinton S. Robbins, Marcel A. Behr, Mihai G. Netea, Philippe Joubert, and Maziar Divangahi.

Read the publication in Cell Reports.

The authors gratefully acknowledge support from the Canadian Institutes of Health Research and the McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding. The authors also thank the teams from the Animal Resources Division (ARD)and the Containment Level 3 (CL3) Platform.