Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines-an exploratory sub-study of the BRACE trial

Nicole L Messina; Susie Germano; Rebecca McElroy; Rhian Bonnici; Branka Grubor-Bauk; David J Lynn; Ellie McDonald; Suellen Nicholson; Kirsten P Perrett; Laure F Pittet; Rajeev Rudraraju; Natalie E Stevens; Kanta Subbarao; Nigel Curtis; BRACE trial

doi:10.1016/j.ebiom.2024.105100

Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines-an exploratory sub-study of the BRACE trial

EBioMedicine. 2024 Apr 23:103:105100. doi: 10.1016/j.ebiom.2024.105100. Online ahead of print.

Authors

Collaborators

BRACE trial:
Nigel Curtis, Andrew Davidson, Kaya Gardiner, Amanda Gwee, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Laure Pittet, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Ellie McDonald, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Nicole Messina, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Laure Pittet, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Veronica Abruzzo, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Simone Barry, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Laurens Manning, Susan Herrmann, Michaela Lucas, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Bruno Jardim, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Julio Croda, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce Dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida Dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes Dos Santos, Claudinalva Ribeiro Dos Santos, Dyenyffer Stéffany Leopoldina Dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora Dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva Dos Santos, Vanessa Cristine de Moraes Dos Santos, Dayane Alves Dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene Dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce Dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Marc Bonten, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M Brakke, Axel Janssen, Marijke A H Koopmans, Toos Lemmens, Titia Leurink, Cristina Prat-Aymerich, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M M L Miranda van Rijen, Margreet Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, Roos Pon, Lieke Preijers, Joke van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap Ten Oever, Rob Ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno Te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores Del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de Las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, John Campbell, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Adilia Warris, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, John Campbell, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, Tamsin Venton

Affiliations

¹ 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. Electronic address: nicole.messina@mcri.edu.au.
² Infectious Diseases Group, Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Parkville, VIC, Australia.
³ Viral Immunology Group, Adelaide Medical School, University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide, SA, Australia.
⁴ 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.
⁵ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁶ 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.
⁷ 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; Paediatric Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁸ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁹ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Elizabeth Street, Melbourne, VIC, Australia.
¹⁰ 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; Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, VIC, Australia.

Abstract

Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens.

Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array.

Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients.

Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study.

Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children's. BRACE trial funding is detailed in acknowledgements.

Keywords: Cytokine; Heterologous immunity; Immunoregulation; Off-target; SARS-CoV-2; Vaccine.