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Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.
Shah, Mihir M; Layhadi, Janice A; Hourcade, Dennis E; Fulton, William T; Tan, Tiak Ju; Dunham, Diane; Chang, Iris; Vel, Monica S; Fernandes, Andrea; Lee, Alexandra S; Liu, James; Arunachalam, Prabhu S; Galli, Stephen J; 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, Stephen R; Fedina, Aleksandra; Gibbs, Bernhard F; Agache, Ioana; Chinthrajah, Sharon; Sindher, Sayantani B; Heider, Anja; Akdis, Cezmi A; Shamji, Mohamed H; Pham, Christine T N; Nadeau, Kari C.
Affiliation
  • Shah MM; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Layhadi JA; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK.
  • Hourcade DE; Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Fulton WT; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK.
  • Tan TJ; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK.
  • Dunham D; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Chang I; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Vel MS; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Fernandes A; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Lee AS; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Liu J; Stanford Health Library, Stanford, California, USA.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA.
  • Galli SJ; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • Boyd SD; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
  • Pulendran B; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
  • Davis MM; Sean N. Parker Center for Allergy & Asthma Research, Stanford, California, USA.
  • O'Hara R; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
  • Park H; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA.
  • Mitchell LM; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
  • Akk A; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
  • Patterson A; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA.
  • Jerath MR; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
  • Monroy JM; Department of Veteran's Administration and Dean's Office, Stanford University, Stanford, California, USA.
  • Ren Z; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
  • Kendall PL; Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Durham SR; Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Fedina A; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Gibbs BF; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Agache I; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Chinthrajah S; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Sindher SB; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Heider A; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK.
  • Akdis CA; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK.
  • Shamji MH; Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
  • Pham CTN; Canterbury Christ Church University, Canterbury, UK.
  • Nadeau KC; Faculty of Medicine, Transilvania University, Brasov, Romania.
Allergy ; 79(9): 2502-2523, 2024 Sep.
Article in En | MEDLINE | ID: mdl-39033312
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Basophils / Complement Activation / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Allergy Year: 2024 Document type: Article Affiliation country: Estados Unidos Country of publication: Dinamarca
Fulltext
Add to My VHL
Print
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Basophils / Complement Activation / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Allergy Year: 2024 Document type: Article Affiliation country: Estados Unidos Country of publication: Dinamarca