Applying lessons learned from nanomedicines to understand rare hypersensitivity reactions to mRNA-based SARS-CoV-2 vaccines

Janos Szebeni, Gert Storm, Julia Y. Ljubimova, Mariana Castells, Elizabeth J. Phillips, Keren Turjeman, Yechezkel Barenholz, Daan J.A. Crommelin, Marina A. Dobrovolskaia*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

83 Scopus citations

Abstract

After over a billion of vaccinations with messenger RNA-lipid nanoparticle (mRNA-LNP) based SARS-CoV-2 vaccines, anaphylaxis and other manifestations of hypersensitivity can be considered as very rare adverse events. Although current recommendations include avoiding a second dose in those with first-dose anaphylaxis, the underlying mechanisms are unknown; therefore, the risk of a future reaction cannot be predicted. Given how important new mRNA constructs will be to address the emergence of new viral variants and viruses, there is an urgent need for clinical approaches that would allow a safe repeated immunization of high-risk individuals and for reliable predictive tools of adverse reactions to mRNA vaccines. In many aspects, anaphylaxis symptoms experienced by the affected vaccine recipients resemble those of infusion reactions to nanomedicines. Here we share lessons learned over a decade of nanomedicine research and discuss the current knowledge about several factors that individually or collectively contribute to infusion reactions to nanomedicines. We aim to use this knowledge to inform the SARS-CoV-2 lipid-nanoparticle-based mRNA vaccine field.

Original languageEnglish
Pages (from-to)337-346
Number of pages10
JournalNature Nanotechnology
Volume17
Issue number4
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
The study was funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract 75N91019D00024 (M.A.D.), a NIH/NCI R01CA206220 grant (J.Y.L.), National Institutes of Health grants P50GM115305, R01HG010863, R01AI152183, R21AI139021 and U01AI154659 (E.J.P.) and NIH contract UAI109565 (E.J.P. and M.C.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. J.S. acknowledges support by the European Union Horizon 2020 projects 825828 (Expert) and 952520 (Biosafety), and the Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary. The Hebrew University received royalties from Barenholz inventions; the Barenholz Fund established with a portion of these royalties is used to support research in the Barenholz Laboratory (Y.B. and K.T.). Funders played no role in any aspect of this review.

Funding Information:
The study was funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract 75N91019D00024 (M.A.D.), a NIH/NCI R01CA206220 grant (J.Y.L.), National Institutes of Health grants P50GM115305, R01HG010863, R01AI152183, R21AI139021 and U01AI154659 (E.J.P.) and NIH contract UAI109565 (E.J.P. and M.C.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. J.S. acknowledges support by the European Union Horizon 2020 projects 825828 (Expert) and 952520 (Biosafety), and the Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary. The Hebrew University received royalties from Barenholz inventions; the Barenholz Fund established with a portion of these royalties is used to support research in the Barenholz Laboratory (Y.B. and K.T.). Funders played no role in any aspect of this review.

Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Keywords

  • Anaphylaxis/etiology
  • COVID-19 Vaccines/adverse effects
  • COVID-19/prevention & control
  • Humans
  • Liposomes
  • Nanomedicine
  • Nanoparticles
  • RNA, Messenger/genetics
  • SARS-CoV-2/genetics
  • Vaccines, Synthetic
  • mRNA Vaccines

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