Single-cell suspensions were prepared from these samples and analyzed for infiltrates using flow cytometry ( Figures 1B and S1A). The LNP-injected skin samples macroscopically showed signs of intense inflammation, such as redness and swelling ( Figure 1A). We sacrificed the mice at different time points post-injection, and ∼1 cm 2 skin samples from the injection sites were collected. We injected 10 μg (4 spots 2.5 μg/spot) of these empty LNPs formulated in phosphate buffered saline (PBS) or control PBS intradermally into adult wild-type (WT) C57BL/6 (B6) mice. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Intradermal and intramuscular 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. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice.
However, the drivers of the reported side effects remain poorly defined.
Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19.
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