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. 2024 Sep;79(9):2502-2523.
doi: 10.1111/all.16231. Epub 2024 Jul 20.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults

Mihir M Shah  1 , Janice A Layhadi  2 , Dennis E Hourcade  3 , William T Fulton  2 , Tiak Ju Tan  2 , Diane Dunham  1 , Iris Chang  1 , Monica S Vel  1 , Andrea Fernandes  1 , Alexandra S Lee  1 , James Liu  4 , Prabhu S Arunachalam  5 , Stephen J Galli  1   6   7 , Scott D Boyd  1   6 , Bali Pulendran  5   6   7 , Mark M Davis  5   7 , Ruth O'Hara  8 , Helen Park  9 , Lynne M Mitchell  3 , Antonina Akk  3 , Alexander Patterson  10 , Maya R Jerath  10 , Jennifer M Monroy  10 , Zhen Ren  10 , Peggy L Kendall  10 , Stephen R Durham  2 , Aleksandra Fedina  2 , Bernhard F Gibbs  11   12 , Ioana Agache  13 , Sharon Chinthrajah  1 , Sayantani B Sindher  1 , Anja Heider  14 , Cezmi A Akdis  14 , Mohamed H Shamji  2 , Christine T N Pham  3 , Kari C Nadeau  15
Affiliations

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults

Mihir M Shah et al. Allergy. 2024 Sep.

Erratum in

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: COVID‐19; COVID‐19 vaccines; SARS‐CoV‐2; mRNA vaccines; polyethylene glycol; vaccine allergy.

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Conflict of interest statement

Competing Interests:

All authors declare no competing financial interests.

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