Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.
Journal article
Shah, M., Layhadi, Janice A, Hourcade, Dennis E, Fulton, W., Tan, Tiak Ju, Dunham, Diane, Chang, I., Vel, Monica S, Fernandes, A., Lee, A., Liu, James, Arunachalam, Prabhu S, Galli, S., Boyd, Scott D, Pulendran, Bali, Davis, Mark M, O'Hara, Ruth, Park, Helen, Mitchell, Lynne M, Akk, Antonina, Patterson, Alexander, Jerath, Maya R, Monroy, Jennifer M, Ren, Zhen, Kendall, Peggy L, Durham, S., Fedina, Aleksandra, Gibbs, Bernhard F, Agache, I., Chinthrajah, S., Sindher, Sayantani B, Heider, Anja, Akdis, C., Shamji, M., Pham, Christine T N and Nadeau, K. 2024. Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults. Allergy. https://doi.org/10.1111/all.16231
| Authors | Shah, M., Layhadi, Janice A, Hourcade, Dennis E, Fulton, W., Tan, Tiak Ju, Dunham, Diane, Chang, I., Vel, Monica S, Fernandes, A., Lee, A., Liu, James, Arunachalam, Prabhu S, Galli, S., Boyd, Scott D, Pulendran, Bali, Davis, Mark M, O'Hara, Ruth, Park, Helen, Mitchell, Lynne M, Akk, Antonina, Patterson, Alexander, Jerath, Maya R, Monroy, Jennifer M, Ren, Zhen, Kendall, Peggy L, Durham, S., Fedina, Aleksandra, Gibbs, Bernhard F, Agache, I., Chinthrajah, S., Sindher, Sayantani B, Heider, Anja, Akdis, C., Shamji, M., Pham, Christine T N and Nadeau, K. |
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| Abstract | During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy. [Abstract copyright: © 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.] |
| Keywords | SARS‐CoV‐2; mRNA vaccines; vaccine allergy; COVID‐19 vaccines; COVID‐19; Polyethylene glycol |
| Year | 2024 |
| Journal | Allergy |
| Publisher | Wiley |
| ISSN | 1398-9995 |
| Digital Object Identifier (DOI) | https://doi.org/10.1111/all.16231 |
| Official URL | https://onlinelibrary.wiley.com/doi/10.1111/all.16231 |
| Funder | NIAMS NIH HHS |
| Publication dates | |
| Online | 20 Jul 2024 |
| Publication process dates | |
| Deposited | 05 Aug 2024 |
| Accepted | 18 Jun 2024 |
| Accepted author manuscript | License |
| Supplemental file | License |
| Output status | Published |
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https://repository.canterbury.ac.uk/item/98929/elucidating-allergic-reaction-mechanisms-in-response-to-sars-cov-2-mrna-vaccination-in-adults
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Accepted author manuscript
Under embargo until 20 Jul 2025
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