1. Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine.
- Author
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Muramatsu H, Lam K, Bajusz C, Laczkó D, Karikó K, Schreiner P, Martin A, Lutwyche P, Heyes J, and Pardi N
- Subjects
- Animals, Freeze Drying, Liposomes, Mice, Nucleosides, RNA, Messenger genetics, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, Influenza Vaccines, Nanoparticles chemistry
- Abstract
Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against the coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can be produced in large quantities. However, the long-term storage of mRNA-LNP vaccines without freezing is still a challenge. Here, we demonstrate that nucleoside-modified mRNA-LNPs can be lyophilized, and the physicochemical properties of the lyophilized material do not significantly change for 12 weeks after storage at room temperature and for at least 24 weeks after storage at 4°C. Importantly, we show in comparative mouse studies that lyophilized firefly luciferase-encoding mRNA-LNPs maintain their high expression, and no decrease in the immunogenicity of a lyophilized influenza virus hemagglutinin-encoding mRNA-LNP vaccine was observed after 12 weeks of storage at room temperature or for at least 24 weeks after storage at 4°C. Our studies offer a potential solution to overcome the long-term storage-related limitations of nucleoside-modified mRNA-LNP vaccines., Competing Interests: Declaration of interests N.P. is named on a patent describing the use of nucleoside-modified mRNA in LNPs as a vaccine platform. He has disclosed those interests fully to the University of Pennsylvania, and he has in place an approved plan for managing any potential conflicts arising from licensing of that patent. K.K. is an employee of BioNTech., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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