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bioRxiv · 10.1101/2023.03.29.534838

Improving mRNA vaccine safety and efficiency with cationized lipid nanoparticle formula

Peng, X.·Liao, G.·Ren, D.·Zhou, Y.·Wu, X.·Lei, Y.·Zhang, Y.·Chen, L.·He, C.·Yin, H.·Yang, G.·Xu, K.
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Abstract

The widespread use of Covid-19 mRNA vaccines has highlighted the need to address rare but concerning side effects. Systemic off-target gene expression has been identified as a primary cause of acute adverse reactions and side effects associated with nucleoside-modified mRNA vaccines. In this study, we incorporated the permanent cationic lipid Dotap component into the mRNA-LNP formula associated with the FDA-approved mRNA vaccine Comirnaty to create a novel positively charged LNP carrier for mRNA vaccine delivery. Using the optimized LNP formula to prepare SARS-Cov-2 Spike mRNA vaccines for immunogenicity testing, Balb/c mice exhibited improved immunogenicity kinetics with initial antibody titers being lower but showing a continuous upward trend, ultimately reaching levels comparable to those of control mRNA vaccines 8 weeks after boost immunization. The mRNA vaccines encapsulated in the modified LNPs have demonstrated a superior safety profile in respect to systemic delivery of LNP constituents, off-target gene expression, and the systemic pro-inflammatory stimulation. Consequently, it may represent a safer alternative of conventional mRNA-LNP vaccines.

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Peng, X., Liao, G., Ren, D., Zhou, Y., Wu, X., Lei, Y., Zhang, Y., Chen, L., He, C., Yin, H., Yang, G., Xu, K.. 2023-03-30. Improving mRNA vaccine safety and efficiency with cationized lipid nanoparticle formula. https://doi.org/10.1101/2023.03.29.534838

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