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

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 Bl...

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Main Authors: Nicole L Messina, Susie Germano, Amy W Chung, Carolien E van deSandt, 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, the BRACE Trial Consortium Group
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Clinical & Translational Immunology
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Online Access:https://doi.org/10.1002/cti2.70023
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author Nicole L Messina
Susie Germano
Amy W Chung
Carolien E van deSandt
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
the BRACE Trial Consortium Group
author_facet Nicole L Messina
Susie Germano
Amy W Chung
Carolien E van deSandt
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
the BRACE Trial Consortium Group
author_sort Nicole L Messina
collection DOAJ
description 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 ex vivo 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.
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spelling doaj-art-bbef406ebbca46a49ccb23eb1d6361942025-01-27T03:44:28ZengWileyClinical & Translational Immunology2050-00682025-01-01141n/an/a10.1002/cti2.70023Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccinationNicole L Messina0Susie Germano1Amy W Chung2Carolien E van deSandt3Natalie E Stevens4Lilith F Allen5Rhian Bonnici6Julio Croda7Claudio Counoupas8Branka Grubor‐Bauk9Ebene R Haycroft10Katherine Kedzierska11Ellie McDonald12Rebecca McElroy13Mihai G Netea14Boris Novakovic15Kirsten P Perrett16Laure F Pittet17Ruth A Purcell18Kanta Subbarao19James A Triccas20David J Lynn21Nigel Curtis22the BRACE Trial Consortium GroupInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaPrecision Medicine Theme South Australian Health and Medical Research Institute Adelaide SA AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaUniversidade Federal de Mato Grosso do Sul‐UFMS Campo Grande MS BrazilSchool of Medical Sciences, Faculty of Medicine and Health The University of Sydney Camperdown NSW AustraliaViral Immunology Group, Adelaide Medical School, Basil Hetzel Institute for Translational Health Research University of Adelaide Adelaide SA AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaDepartment of Internal Medicine and Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The NetherlandsDepartment of Paediatrics The University of Melbourne Parkville VIC AustraliaDepartment of Paediatrics The University of Melbourne Parkville VIC AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville VIC AustraliaSchool of Medical Sciences, Faculty of Medicine and Health The University of Sydney Camperdown NSW AustraliaPrecision Medicine Theme South Australian Health and Medical Research Institute Adelaide SA AustraliaInfectious Diseases Group, Infection, Immunity and Global Health Theme Murdoch Children's Research Institute Parkville VIC AustraliaAbstract 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 ex vivo 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.https://doi.org/10.1002/cti2.70023Bacille Calmette–Guérin (BCG) vaccineCOVID‐19heterologousimmunityimmunomodulation
spellingShingle Nicole L Messina
Susie Germano
Amy W Chung
Carolien E van deSandt
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
the BRACE Trial Consortium Group
Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
Clinical & Translational Immunology
Bacille Calmette–Guérin (BCG) vaccine
COVID‐19
heterologous
immunity
immunomodulation
title Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
title_full Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
title_fullStr Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
title_full_unstemmed Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
title_short Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2 and COVID‐19 vaccination
title_sort effect of bacille calmette guerin vaccination on immune responses to sars cov 2 and covid 19 vaccination
topic Bacille Calmette–Guérin (BCG) vaccine
COVID‐19
heterologous
immunity
immunomodulation
url https://doi.org/10.1002/cti2.70023
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