@article{10902/35987,
year = {2024},
url = {https://hdl.handle.net/10902/35987},
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.},
organization = {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. Acknowledgements We thank the BRACE trial and particularly the BCOS sub-study participants, as well as the site and central personnel who assisted with the trial (detailed in Supplementary Appendix). We thank Cecilia Moore for advice on the statistical analysis approach for this sub-study. Funding: The BRACE trial is supported by the Bill & Melinda Gates Foundation [INV-017302], the Minderoo Foundation [COV001], Sarah and Lachlan Murdoch, the Royal Children’s Hospital Foundation [2020-1263 BRACE Trial], Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare and individual donors. The Murdoch Children’s Research Institute (MCRI) leads the BRACE trial across 36 sites in five countries. It is supported by the Victorian Government’s Operational Infrastructure Support Programme. NC is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (GNT1197117). LFP is supported by the Swiss National Science Foundation (Early Postdoc Mobility Grant, P2GEP3_178155). K.P.P is supported by a NHMRC Investigator Grant (GNT2008911) and a Melbourne Children’s Clinician-Scientist Fellowship. KS is supported by a NHMRC Investigator Grant (APP1177174). BGB is supported by The Hospital Research Foundation. NLM and sample analysis in this study are also supported by an NHMRC Ideas grant (GNT2012769).},
publisher = {Elsevier},
publisher = {EBioMedicine, 2024, 103, 105100},
title = {Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines-an exploratory sub-study of the BRACE trial},
author = {Messina, Nicole L. and Germano, Susie and McElroy, Rebecca and Bonnici, Rhian and Grubor Bauk, Branka and Lynn, David J. and McDonald, Ellie A. and Nicholson, Suellen R. and Perrett, Kirsten P. and Pittet, Laure F. and Rudraraju, Rajeev and Stevens, Natalie E. and Kanta Subbarao and Curtis, Nigel C. and Davidson, Andrew and Gardiner, Kaya and Gwee, Amanda and Fariñas Álvarez, María del Carmen and Gutiérrez Cuadra, Manuel and Arnaiz de las Revillas Almajano, Francisco},
}