To the Editor:
Thank you for the correspondence of Borgsteede et al “Other excipients
than PEG might cause serious hypersensitivity reactions in COVID-19
vaccines”.1
We agree with the authors and their observations indicating that other
components different from polyethylene glycol (PEG) in the vaccines
currently available for the prevention of COVID-19 could also have a
potential role in hypersensitivity reactions described. In our
editorial, we focused on BNT162b2 vaccine developed by BioNTech and
Pfizer given special attention to the excipient PEG 2000 g/mol
(PEG-2000) contained in the vaccine in form of a PEGylated micellar
carrier as a potential culprit of the reported anaphylactic reactions.
PEG-2000 is among the excipients from BNT162b2 the most likely to
produce an allergic response. As we focused on the first developed
COVID-19 vaccine, our first editorial did not cover other vaccines
developed for COVID-19. In that regard, we have recently pointed out in
a follow-up article that the excipient tromethamine (also named
trometamol) contained in the Moderna mRNA-1273 vaccine could contribute
to the induction of anaphylactic reactions in sensitized individuals as
well.2 As Borgsteede et al1 and
ourselves2 indicated, a recent article has reported
the first case of anaphylaxis to trometamol as an ingredient in a
gadolinium-based contrast agent (GBCA). The reaction was induced shortly
after the injection of GBCA and an IgE-mediated mechanism against
trometamol could be detected.3 Although both BNT162b2
and mRNA-1273 vaccines are mRNA vaccines containing PEG-2000, the
excipient tromethamine is exclusive from the latter (Figure 1).
The third vaccine for the prevention of COVID-19 has been recently
approved in the United Kingdom. The vaccine, named AZD1222, developed by
Oxford University and AstraZeneca, consists of a replication-deficient
chimpanzee adenovirus (ChAdOx1) vector that contains the gene of the
glycoprotein spike (S) antigen of SARS-CoV-2. Although the AZD1222 DNA
vaccine does not contain PEG-2000 or other PEGs with different molecular
weights, as Borgsteede et al pointed out,1 it does
contain the structurally related compound polyoxyethylene-80-sorbitan
monooleate or polysorbate 80 (also named Tween 80) (Figure 1). The
cross-reactivity between polysorbate 80 and PEGs seems to be due to a
shared moiety
–(CH2CH2O)ncontained in both compounds. Polysorbate 80 is widely used as an
emulsifier and stabilizer in the food industry and it is also a common
excipient in medications and vaccines such as influenza, Hepatitis B,
Human papillomavirus (HPV) vaccines, with the function of facilitating
the vaccine components to stay soluble. Polysorbates 20, 40, and 60 also
exist. Polysorbates 80 and 20 have also been included as excipients in
other SARS-CoV-2 vaccines currently under evaluation in phases I, II, or
III trials and that are based on adenovirus vectors or on the
recombinant glycoprotein (S) spike antigen.4 Up to
date, most of the cases of allergic reactions to polysorbates have been
associated with medicines containing this excipient and only a few cases
of allergy to vaccines due to polysorbates have been
reported.5,6 The cases could be underrepresented due
to the general unawareness among physicians of the allergenic potential
of excipients such as polysorbates that may be behind an unclear
allergic reaction to a given vaccine.
The role of other vaccines components such as
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or EDTA as potential
triggers of hypersensitivity reactions should also be considered (Figure
1).
Although in general terms allergic reactions to vaccines are rare, the
fact that the newly developed vaccines for the prevention of COVID-19
will be applied to a considerable majority of the world population,
makes it important for health care providers to be aware of the
potential threat of the excipients from COVID-19 vaccines with the
potential to produce hypersensitivity reactions before the
administration of the vaccines.
Beatriz Cabanillas1
Cezmi A. Akdis2,3
Natalija Novak4*
1Department of Allergy, Research Institute Hospital
Doce de Octubre, Madrid, Spain
2Swiss Institute of Allergy and Asthma Research
(SIAF), University of Zurich, Davos, Switzerland.
3Christine Kühne-Center for Allergy Research and
Education, Davos, Switzerland
4Department of Dermatology and Allergy, University
Hospital Bonn, Bonn, Germany.
*Corresponding author: Univ.-Prof. Dr. Natalija Novak
Department of Dermatology and Allergy, University Hospital, Bonn,
Venusberg Campus 1, 53127 Bonn, Germany.
Email:
natalija.novak@ukbonn.de