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ID 117846
Author
Suzuki, Yuta Eisai
Miyazaki, Takayuki Eisai
Muto, Hiroki Eisai
Kubara, Kenji Eisai
Mukai, Yohei KAN Research Institute
Watari, Ryuji Eisai
Sato, Shinya Eisai
Kondo, Keita Eisai
Ito, Masashi Eisai
Tsukahara, Kappei Eisai
Content Type
Journal Article
Description
mRNA and lipid nanoparticles have emerged as powerful systems for the preparation of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The emergence of novel variants or the necessity of cold chain logistics for approved mRNA vaccines undermines the investigation of next-generation systems that could preserve both potency and stability. However, the correlation between lipid nanoparticle composition and activity is not fully explored. Here, we screened a panel of ionizable lipids in vivo and identified lead lipid nanoparticles with a branched-tail lipid structure. Buffer optimization allowed the determination of lyophilization conditions, where lipid nanoparticle-encapsulated mRNA encoding SARS-CoV-2 spike protein could induce robust immunogenicity in mice after 1 month of storage at 5°C and 25°C. Intramuscularly injected lipid nanoparticles distributed in conventional dendritic cells in mouse lymph nodes induced balanced T helper (Th) 1/Th2 responses against SARS-CoV-2 spike protein. In nonhuman primates, two doses of 10 or 100 μg of mRNA induced higher spike-specific binding geometric mean titers than those from a panel of SARS-CoV-2-convalescent human sera. Immunized sera broadly inhibited the viral entry receptor angiotensin-converting enzyme 2 (ACE2) from binding to the spike protein in all six strains tested, including variants of concern. These results could provide useful information for designing next-generation mRNA vaccines.
Journal Title
Molecular Therapy - Nucleic Acids
ISSN
21622531
Publisher
The American Society of Gene and Cell Therapy|Elsevier
Volume
30
Start Page
226
End Page
240
Published Date
2022-09-24
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences