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

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.

Automated summary

After over a billion vaccinations with mRNA-LNP based SARS-CoV-2 vaccines, anaphylaxis and hypersensitivity reactions are considered rare adverse events. The underlying mechanisms of first-dose anaphylaxis and the predictability of future reactions are unknown. Given the importance of new mRNA constructs in addressing emerging viral variants, there is a need for safe repeated immunization approaches for high-risk individuals and reliable predictive tools for adverse reactions to mRNA vaccines. Lessons from nanomedicine research on infusion reactions can inform the mRNA vaccine field.