Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov;76(11):3307-3313.
doi: 10.1111/all.14794. Epub 2021 Jun 17.

Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation

Ludger Klimek  1 , Natalija Novak  2 , Beatriz Cabanillas  3 , Marek Jutel  4 , Jean Bousquet  5   6 , Cezmi A Akdis  7
Affiliations
Review

Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation

Ludger Klimek et al. Allergy. 2021 Nov.

Abstract

Following the emergency use authorization of the mRNA-1273 vaccine on the 18th of December 2020, two mRNA vaccines are in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase III pivotal trials excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and the United States, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000)-contained in both vaccines as the PEG-micellar carrier system-as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated, but may also result from complement activation-related pseudoallergy (CARPA) that has been described in similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such as gadolinium-based contrast media. Skin prick, intradermal and epicutaneous tests, in vitro sIgE assessment, evaluation of sIgG/IgM, and basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.

Keywords: COVID; SARS-CoV; vaccines.

PubMed Disclaimer

Conflict of interest statement

Dr. Akdis reports grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne—Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, Scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in Scibase. Dr. Bousquet reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Purina, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed Innov, outside the submitted work. Dr. Jutel reports personal fees from ALK‐Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, HAL, during the conduct of the study; Astra‐Zeneka, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Janssen, Medimmune, Chiesi, outside the submitted work. Dr. Klimek reports grants and/or personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, ALK‐Abelló, from LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk, Cassella med, outside the submitted work; and reports Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinischeImmunologie, HNO‐BV, GPA, EAACI. Dr. Novak reports grants and/or personal fees from ALK‐Abello, HAL Allergy, Stallergenes Geer, Leti Pharma, Novartis, Leo Pharma, Abbvie, Sanofi Genzmye, Lofarma, Bencard Allergy Therapeutics, outside the submitted work. Dr. Cabanillas has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Representation of the Moderna COVID‐19 vaccine: The principle of the PEGylated‐lipid nanoparticles as a delivery system for the mRNA is illustrated together with the full list of ingredients contained in the vaccine. PEG‐2000 and tromethamine/trometamol as potential triggers of allergic reactions are indicated in red and shown on the left side. Different ways of exposition to PEG and PEG analogues are illustrated on the right side. Biorender software was used to create the figure under an academic license
FIGURE 2
FIGURE 2
Algorithm for vaccination with the Moderna vaccine mRNA‐1273 (modified according to Ref. [58])
See this image and copyright information in PMC

References

    1. FDA . United States Food and Drug Administration (FDA). Emergency use authorization for Moderna COVIC‐19 vaccine. https://www.FDA.gov/media/144636/download. Accessed December 28, 2020.
    1. FDA . United States Food and Drug Administration (FDA). Emergency use authorization for Pfizer‐BioNTech COVID‑19 Vaccine. https://www.fda.gov/media/144412/download. Accessed December 28, 2020.
    1. Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS‐CoV‐2 mRNA‐1273 vaccine in older adults. N Engl J Med. 2020;383(25):2427‐2438. - PMC - PubMed
    1. Widge AT, Rouphael NG, Jackson LA, et al. Durability of responses after SARS‐CoV‐2 mRNA‐1273 vaccination. N Engl J Med. 2021;384(1):80‐82. - PMC - PubMed
    1. Moderna I. Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID‐19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization. 30 November 2020. Cambridge, UK: Moderna, Inc.; 2020.