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
Tsukumo, Shin-ichi
Tokushima University
Tokushima University Educator and Researcher Directory
KAKEN Search Researchers
Yasutomo, Koji
Tokushima University
Tokushima University Educator and Researcher Directory
KAKEN Search Researchers
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/).
|
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
|
TextVersion |
Publisher
|
departments |
Medical Sciences
|