TY - JOUR
T1 - Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination
AU - Messina, Nicole L.
AU - Germano, Susie
AU - Chung, Amy W.
AU - van de Sandt, Carolien E.
AU - Stevens, Natalie E.
AU - Allen, Lilith F.
AU - Bonnici, Rhian
AU - Croda, Julio
AU - Counoupas, Claudio
AU - Grubor-Bauk, Branka
AU - Haycroft, Ebene R.
AU - Kedzierska, Katherine
AU - McDonald, Ellie
AU - McElroy, Rebecca
AU - Netea, Mihai G.
AU - Novakovic, Boris
AU - Perrett, Kirsten
AU - Pittet, Laure F.
AU - Purcell, Ruth A.
AU - Subbarao, Kanta
AU - Triccas, James A.
AU - Lynn, David J.
AU - Curtis, Nigel
AU - the BRACE Trial Consortium Group
AU - Davidson, Andrew
AU - Gardiner, Kaya
AU - Gwee, Amanda
AU - Jamieson, Tenaya
AU - Morawakage, Thilanka
AU - Perlen, Susan
AU - Sastry, Amber
AU - Teo, Jia Wei
AU - Orsini, Francesca
AU - Lee, Katherine
AU - Moore, Cecilia
AU - Vidmar, Suzanna
AU - Ali, Rashida
AU - Dunn, Ross
AU - Edler, Peta
AU - Gell, Grace
AU - Goodall, Casey
AU - Hall, Richard
AU - Krastev, Ann
AU - La, Nathan
AU - McPhate, Nick
AU - Nguyen, Thao
AU - Ren, Jack
AU - Stevens, Luke
AU - Alamrousi, Ahmed
AU - Dang, Thanh
AU - Hua, Jenny
AU - Razmovska, Monica
AU - Reddiex, Scott
AU - Wang, Xiaofang
AU - Anderson, Jeremy
AU - Azzopardi, Kristy
AU - Bennett-Wood, Vicki
AU - Czajko, Anna
AU - Mazarakis, Nadia
AU - McCafferty, Conor
AU - Oppedisano, Frances
AU - Ortika, Belinda
AU - Pell, Casey
AU - Spry, Leena
AU - Toh, Ryan
AU - Velagapudi, Sunitha
AU - Vlahos, Amanda
AU - Wee-Hee, Ashleigh
AU - Ramos, Pedro
AU - De La Cruz, Karina
AU - Gamage, Dinusha
AU - Karunanayake, Anushka
AU - Mezzetti, Isabella
AU - Ong, Benjamin
AU - Singh, Ronita
AU - Sooriyarachchi, Enoshini
AU - Nicholson, Suellen
AU - Cain, Natalie
AU - Brizuela, Rianne
AU - Huang, Han
AU - Abruzzo, Veronica
AU - Bealing, Morgan
AU - Bimboese, Patricia
AU - Bowes, Kirsty
AU - Burrell, Emma
AU - Chan, Joyce
AU - Cushnahan, Jac
AU - Elborough, Hannah
AU - Elkington, Olivia
AU - Fahey, Kieran
AU - Fernandez, Monique
AU - Flynn, Catherine
AU - Fowler, Sarah
AU - Andrit, Marie Gentile
AU - Gladanac, Bojana
AU - Hammond, Catherine
AU - Ma, Norine
AU - Macalister, Sam
AU - Milojevic, Emmah
AU - Mojeed, Jesutofunmi
AU - Nguyen, Jill
AU - O'Donnell, Liz
AU - Olivier, Nadia
AU - Ooi, Isabelle
AU - Reynolds, Stephanie
AU - Shen, Lisa
AU - Sherry, Barb
AU - Spotswood, Judith
AU - Wedderburn, Jamie
AU - Younes, Angela
AU - Legge, Donna
AU - Bell, Jason
AU - Cheah, Jo
AU - Cobbledick, Annie
AU - Lim, Kee
AU - Elia, Sonja
AU - Addlem, Lynne
AU - Bourke, Anna
AU - Brophy, Clare
AU - Henare, Nadine
AU - Jenkins, Narelle
AU - Machingaifa, Francesca
AU - Miller, Skye
AU - Mitchell, Kirsten
AU - Pitkin, Sigrid
AU - Wall, Kate
AU - Villanueva, Paola
AU - Crawford, Nigel
AU - Norton, Wendy
AU - Tan, Niki
AU - Chengodu, Thilakavathi
AU - Dawson, Diane
AU - Gordon, Victoria
AU - Korman, Tony
AU - O'Bryan, Jess
AU - Abruzzo, Veronica
AU - Agius, Sophie
AU - Bannister, Samantha
AU - Bucholc, Jess
AU - Burns, Alison
AU - Camesella, Beatriz
AU - Carlin, John
AU - Ciaverella, Marianna
AU - Curtis, Maxwell
AU - Firth, Stephanie
AU - Guo, Christina
AU - Hannan, Matthew
AU - Hill, Erin
AU - Joshi, Sri
AU - Lieschke, Katherine
AU - Mathers, Megan
AU - Odoi, Sasha
AU - Rak, Ashleigh
AU - Richards, Chris
AU - Steve, Leah
AU - Stewart, Carolyn
AU - Sudbury, Eva
AU - Thomson, Helen
AU - Watts, Emma
AU - Williams, Fiona
AU - Young, Angela
AU - Glenn, Penny
AU - Kaynes, Andrew
AU - De Floy, Amandine Philippart
AU - Buchanan, Sandy
AU - Sondag, Thijs
AU - Xie, Ivy
AU - Edmund, Harriet
AU - Byrne, Bridie
AU - Keeble, Tom
AU - Ngien, Belle
AU - Noonan, Fran
AU - Wearing-Smith, Michelle
AU - Clarke, Alison
AU - Davies, Pemma
AU - Eastwood, Oliver
AU - Ellinghaus, Alric
AU - Ghieh, Rachid
AU - Hilton, Zahra
AU - Jennings, Emma
AU - Kakkos, Athina
AU - Liang, Iris
AU - Nicol, Katie
AU - O'Callaghan, Sally
AU - Osman, Helen
AU - Rajaram, Gowri
AU - Ratcliffe, Sophia
AU - Rayner, Victoria
AU - Salmon, Ashleigh
AU - Scheppokat, Angela
AU - Stevens, Aimee
AU - Street, Rebekah
AU - Toogood, Nicholas
AU - Wood, Nicholas
AU - Bahaduri, Twinkle
AU - Baulman, Therese
AU - Byrne, Jennifer
AU - Carter, Candace
AU - Corbett, Mary
AU - Dao, Aiken
AU - Desylva, Maria
AU - Dunn, Andrew
AU - Gardiner, Evangeline
AU - Joyce, Rosemary
AU - Kandasamy, Rama
AU - Munns, Craig
AU - Pelayo, Lisa
AU - Sharma, Ketaki
AU - Sterling, Katrina
AU - Uren, Caitlin
AU - Colaco, Clinton
AU - Douglas, Mark
AU - Hamilton, Kate
AU - Bartlett, Adam
AU - McMullan, Brendan
AU - Palasanthiran, Pamela
AU - Williams, Phoebe
AU - Beardsley, Justin
AU - Bergant, Nikki
AU - Lagunday, Renier
AU - Overton, Kristen
AU - Post, Jeffrey
AU - Al-Hindawi, Yasmeen
AU - Barney, Sarah
AU - Byrne, Anthony
AU - Mead, Lee
AU - Plit, Marshall
AU - Benson, Saoirse
AU - Blake, Stephen
AU - Botten, Rochelle
AU - Chern, Tee Yee
AU - Eden, Georgina
AU - Griffith, Liddy
AU - James, Jane
AU - Lynn, Miriam
AU - Markow, Angela
AU - Sacca, Domenic
AU - Wesselingh, Steve
AU - Doran, Catriona
AU - Barry, Simone
AU - Sawka, Alice
PY - 2025/1/25
Y1 - 2025/1/25
N2 - 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.
AB - 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.
KW - Bacille Calmette–Guérin (BCG) vaccine
KW - COVID-19
KW - heterologous
KW - immunity
KW - immunomodulation
UR - http://www.scopus.com/inward/record.url?scp=85216892210&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/2012769
UR - http://purl.org/au-research/grants/NHMRC/2008092
UR - http://purl.org/au-research/grants/NHMRC/1173871
U2 - 10.1002/cti2.70023
DO - 10.1002/cti2.70023
M3 - Article
AN - SCOPUS:85216892210
SN - 2050-0068
VL - 14
JO - Clinical and Translational Immunology
JF - Clinical and Translational Immunology
IS - 1
M1 - e70023
ER -