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Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates
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 investigati...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508692/ https://www.ncbi.nlm.nih.gov/pubmed/36187052 http://dx.doi.org/10.1016/j.omtn.2022.09.017 |
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author | Suzuki, Yuta Miyazaki, Takayuki Muto, Hiroki Kubara, Kenji Mukai, Yohei Watari, Ryuji Sato, Shinya Kondo, Keita Tsukumo, Shin-ichi Yasutomo, Koji Ito, Masashi Tsukahara, Kappei |
author_facet | Suzuki, Yuta Miyazaki, Takayuki Muto, Hiroki Kubara, Kenji Mukai, Yohei Watari, Ryuji Sato, Shinya Kondo, Keita Tsukumo, Shin-ichi Yasutomo, Koji Ito, Masashi Tsukahara, Kappei |
author_sort | Suzuki, Yuta |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9508692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-95086922022-09-26 Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates Suzuki, Yuta Miyazaki, Takayuki Muto, Hiroki Kubara, Kenji Mukai, Yohei Watari, Ryuji Sato, Shinya Kondo, Keita Tsukumo, Shin-ichi Yasutomo, Koji Ito, Masashi Tsukahara, Kappei Mol Ther Nucleic Acids Original Article 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. American Society of Gene & Cell Therapy 2022-09-24 /pmc/articles/PMC9508692/ /pubmed/36187052 http://dx.doi.org/10.1016/j.omtn.2022.09.017 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Suzuki, Yuta Miyazaki, Takayuki Muto, Hiroki Kubara, Kenji Mukai, Yohei Watari, Ryuji Sato, Shinya Kondo, Keita Tsukumo, Shin-ichi Yasutomo, Koji Ito, Masashi Tsukahara, Kappei Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title | Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title_full | Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title_fullStr | Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title_full_unstemmed | Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title_short | Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates |
title_sort | design and lyophilization of lipid nanoparticles for mrna vaccine and its robust immune response in mice and nonhuman primates |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508692/ https://www.ncbi.nlm.nih.gov/pubmed/36187052 http://dx.doi.org/10.1016/j.omtn.2022.09.017 |
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