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https://www.arca.fiocruz.br/handle/icict/68723
EFFECT OF BACILLE CALMETTE-GUÉRIN VACCINATION ON IMMUNE RESPONSES TO SARS-COV-2 AND COVID-19 VACCINATION
Author
Messina, Nicole L.
Germano, Susie
Chung, Amy W.
Sandt, Carolien E. van de
Stevens, Natalie E.
Allen, Lilith F.
Bonnici, Rhian
Croda, Julio
Counoupas, Claudio
Grubor-Bauk, Branka
Haycroft, Ebene R.
Kedzierska, Katherine
McDonald, Ellie
McElroy, Rebecca
Netea, Mihai G.
Novakovic, Boris
Perrett, Kirsten P.
Pittet, Laure F.
Purcell, Ruth A.
Subbarao, Kanta
Triccas, James A.
Lynn, David J.
Curtis, Nigel
Germano, Susie
Chung, Amy W.
Sandt, Carolien E. van de
Stevens, Natalie E.
Allen, Lilith F.
Bonnici, Rhian
Croda, Julio
Counoupas, Claudio
Grubor-Bauk, Branka
Haycroft, Ebene R.
Kedzierska, Katherine
McDonald, Ellie
McElroy, Rebecca
Netea, Mihai G.
Novakovic, Boris
Perrett, Kirsten P.
Pittet, Laure F.
Purcell, Ruth A.
Subbarao, Kanta
Triccas, James A.
Lynn, David J.
Curtis, Nigel
Affilliation
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. 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.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Fundação Oswaldo Cruz. Fiocruz Mato Grosso do Sul. Campo Grande, MS, Brasil / Universidade Federal de Mato Grosso do Sul. Campo Grande, MS, Brasil / 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.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, 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.
Department of Paediatrics. The University of Melbourne. Parkville, VIC, Australia / Molecular Immunity Group, Infection and Immunity Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Department of Paediatrics. The University of Melbourne. 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.
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 / Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit. Geneva University Hospitals and Faculty of Medicine. Geneva, Switzerland.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
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.
Precision Medicine Theme. South Australian Health and Medical Research Institute. Adelaide, SA, Australia.
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 Infectious Diseases. The Royal Children's Hospital Melbourne. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. 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.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Fundação Oswaldo Cruz. Fiocruz Mato Grosso do Sul. Campo Grande, MS, Brasil / Universidade Federal de Mato Grosso do Sul. Campo Grande, MS, Brasil / 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.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Infectious Diseases Group, Infection, Immunity and Global Health Theme. Murdoch Children's Research Institute. Parkville, VIC, 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.
Department of Paediatrics. The University of Melbourne. Parkville, VIC, Australia / Molecular Immunity Group, Infection and Immunity Theme. Murdoch Children's Research Institute. Parkville, VIC, Australia.
Department of Paediatrics. The University of Melbourne. 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.
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 / Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit. Geneva University Hospitals and Faculty of Medicine. Geneva, Switzerland.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
The University of Melbourne. The Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Parkville, VIC, Australia.
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.
Precision Medicine Theme. South Australian Health and Medical Research Institute. Adelaide, SA, Australia.
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 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 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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