PT  - JOURNAL ARTICLE
AU  - Sonia Ndeupen
AU  - Zhen Qin
AU  - Sonya Jacobsen
AU  - Henri Estanbouli
AU  - Aurélie Bouteau
AU  - Botond Z. Igyártó
TI  - The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
AID  - 10.1101/2021.03.04.430128
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.04.430128
4099  - http://biorxiv.org/content/early/2021/07/23/2021.03.04.430128.short
4100  - http://biorxiv.org/content/early/2021/07/23/2021.03.04.430128.full
AB  - Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against coronavirus disease in 2019 (COVID-19). Clinical trials and ongoing vaccinations present with very high protection levels and varying degrees of side effects. However, the nature of the reported side effects remains poorly defined. Here we present evidence that LNPs used in many preclinical studies are highly inflammatory in mice. Intradermal injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate.In summary, here we show that the LNPs used for many preclinical studies are highly inflammatory. Thus, their potent adjuvant activity and reported superiority comparing to other adjuvants in supporting the induction of adaptive immune responses likely stem from their inflammatory nature. Furthermore, the preclinical LNPs are similar to the ones used for human vaccines, which could also explain the observed side effects in humans using this platform.Competing Interest StatementThe authors have declared no competing interest.