Anti-PEG antibodies before and after a first dose of Comirnaty® (mRNA-LNP-based SARS-CoV-2 vaccine)

Yaelle Bavli*, Bing Mae Chen, Guy Gross, Alon Hershko, Keren Turjeman, Steve Roffler, Yechezkel Barenholz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The early and massive vaccination campaign in Israel with the mRNA-LNP Comirnaty® (Pfizer-BioNTech) vaccine against the SARS-CoV-2 virus made available large amounts of data regarding the efficacy and safety of this vaccine. Adverse reactions to mRNA-based SARS-CoV-2 vaccines are rare events, but due to large mediatic coverage they became feared and acted as a potential source of delay for the vaccination of the Israeli population. The experience with the reactogenicity of the polyethylene glycol (PEG) moiety of PEGylated liposomes, PEGylated proteins and other PEGylated drugs raised the fear that similar adverse effects can be associated with the PEG lipid which is an essential component of currently used mRNA-LNP vaccines against COVID-19. In this study we quantified the levels of anti-PEG IgG, IgM and IgE present in the blood of 79 volunteers immediately before and 3 weeks after receiving a first dose of Comirnaty® vaccine. Our in vitro results show that different humanized anti-PEG antibodies bind the PEGylated nano-liposomes in a concentration-dependent manner, but they bind with a lower affinity to the Comirnaty vaccine, despite it having a high mole% of neutral PEG2000-lipid on its surface. We found an increase in IgG concentration in the blood 3 weeks after the first vaccine administration, but no increase in IgM or IgE. In addition, no severe signs of adverse reactions to the Comirnaty vaccine were observed in the population studied despite the significant pre-existing high titers of IgG before the first dose of vaccine in 2 donors.

Original languageAmerican English
Pages (from-to)316-322
Number of pages7
JournalJournal of Controlled Release
StatePublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.


  • Anti-PEG antibodies
  • COVID-19 vaccine
  • LNP
  • PEG
  • mRNA-based SARS-CoV-2 vaccine


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