Journal Article Epublish 34 citations
PubMed: 35573165 DOI: 10.1002/cti2.1387
Off-target effects of bacillus Calmette-Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19.
Clin Transl Immunology 11(4):e1387
Authors: Nicole L Messina, Susie Germano, Rebecca McElroy, Rajeev Rudraraju, Rhian Bonnici, Laure F Pittet, Melanie R Neeland, Suellen Nicholson, Kanta Subbarao, Nigel Curtis
Affiliations
- Infectious Diseases Group, Infection and Immunity Theme Murdoch Children's Research Institute Parkville VIC Australia.
- Department of Paediatrics The University of Melbourne Parkville VIC Australia.
- Department of Microbiology and Immunology University of Melbourne at The Peter Doherty Institute for Infection and Immunity Parkville VIC Australia.
- Paediatric Infectious Diseases Unit Faculty of Medicine Geneva University Hospitals Geneva Switzerland.
- Molecular Immunity Group, Infection and Immunity Theme Murdoch Children's Research Institute Parkville VIC Australia.
- Victorian Infectious Diseases Reference Laboratory The Royal Melbourne Hospital The Peter Doherty Institute for Infection and Immunity Parkville VIC Australia.
- WHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity Parkville VIC Australia.
- Infectious Diseases The Royal Children's Hospital Melbourne Parkville VIC Australia.
Abstract
Background and objectives
Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette-Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on immune responses to SARS-CoV-2.
Methods
This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry.
Results
BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4 and CD8 T cells, and an activation of eosinophils in response to SARS-CoV-2.
Conclusions
The immunomodulatory signature of BCG's off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.
MeSH
Cytokines, Cells, Sars-Cov-2, Blood, Vaccines, Bacillus, Vaccination, Covid-19, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus
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