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Publications

Journal Article Epublish 1 citation

PubMed: 39872402 DOI: 10.1002/cti2.70023

Effect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.

Clin Transl Immunology 14(1):e70023

Authors: Nicole L Messina, Susie Germano, Amy W Chung, Carolien E van de Sandt, Natalie E Stevens, Lilith F Allen, Rhian Bonnici, Julio Croda, Claudio Counoupas, Branka Grubor-Bauk, Ebene R Haycroft, Katherine Kedzierska, Ellie McDonald, Rebecca McElroy, Mihai G Netea, Boris Novakovic, Kirsten P Perrett, Laure F Pittet, Ruth A Purcell, Kanta Subbarao, James A Triccas, David J Lynn, Nigel Curtis

Affiliations

  • Infectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC Australia.
  • Department of Paediatrics The University of Melbourne Parkville VIC Australia.
  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC Australia.
  • Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide SA Australia.
  • Flinders Health and Medical Research Institute Flinders University Bedford Park SA Australia.
  • Universidade Federal de Mato Grosso do Sul-UFMS Campo Grande MS Brazil.
  • Fiocruz Mato Grosso do Sul Fundação Oswaldo Cruz Campo Grande MS Brazil.
  • Department of Epidemiology of Microbial Diseases Yale School of Public Health New Haven CT USA.
  • School of Medical Sciences, Faculty of Medicine and Health The University of Sydney Camperdown NSW Australia.
  • Sydney Institute for Infectious Diseases and the Charles Perkins Centre The University of Sydney Camperdown NSW Australia.
  • Centre for Infection and Immunity Centenary Institute Camperdown NSW Australia.
  • Viral Immunology Group, Adelaide Medical School, Basil Hetzel Institute for Translational Health Research University of Adelaide Adelaide SA Australia.
  • Department of Internal Medicine and Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands.
  • Department for Immunology and Metabolism, Life and Medical Sciences Institute University of Bonn Bonn Germany.
  • Molecular Immunity Group, Infection and Immunity Theme Murdoch Children's Research Institute Parkville VIC Australia.
  • Population Allergy Group Murdoch Children's Research Institute Parkville VIC Australia.
  • Department of Allergy and Immunology The Royal Children's Hospital Melbourne Parkville VIC Australia.
  • Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit Geneva University Hospitals and Faculty of Medicine Geneva Switzerland.
  • Department of Infectious Diseases The Royal Children's Hospital Melbourne Parkville VIC Australia.

Abstract

Objectives

Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods

Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination. SARS-CoV-2-specific antibodies were measured using ELISA and multiplex bead array, whole blood cytokine responses to γ-irradiated SARS-CoV-2 (iSARS) stimulation were measured by multiplex bead array, and SARS-CoV-2-specific T-cell responses were measured by activation-induced marker and intracellular cytokine staining assays.

Results

After randomisation (mean 11 months) but prior to COVID-19 vaccination, the BCG group had lower cytokine responses to iSARS stimulation than the Control group. After two doses of ChAdOx1-S, differences in iSARS-induced cytokine responses between the BCG group and Control group were found for three cytokines (CTACK, TRAIL and VEGF). No differences were found between the groups after BNT162b2 vaccination. There were also no differences between the BCG and Control groups in COVID-19 vaccine-induced antigen-specific antibody responses, T-cell activation or T-cell cytokine production.

Conclusion

BCG vaccination induced a broad and persistent reduction in cytokine responses to SARS-CoV-2. Following COVID-19 vaccination, this effect was abrogated, and BCG vaccination did not influence adaptive immune responses to COVID-19 vaccine antigens.

MeSH

Cytokines, Cells, Sars-Cov-2, Immunomodulation, Vaccines, Vaccination, Covid-19, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus

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