| Item type |
文献 / Documents(1) |
| 公開日 |
2023-02-09 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.omtn.2022.09.017 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1016/j.omtn.2022.09.017 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
|
言語 |
en |
| 著者 |
スズキ, ユウタ
ミヤザキ, タカユキ
ムトウ, ヒロキ
クバラ, ケンジ
ムカイ, ヨウヘイ
ワタリ, リュウジ
サトウ, シンヤ
コンドウ, ケイタ
九十九, 伸一
安友, 康二
イトウ, マサシ
ツカハラ, カッペイ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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. |
|
言語 |
en |
| 書誌情報 |
en : Molecular Therapy - Nucleic Acids
巻 30,
p. 226-240,
発行日 2022-09-24
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
21622531 |
| 出版者 |
|
|
出版者 |
The American Society of Gene and Cell Therapy |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| EID |
|
|
識別子 |
392461 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
mtna_30_226.pdf (2.67 MB)
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