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Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses
Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659346/ https://www.ncbi.nlm.nih.gov/pubmed/36322769 http://dx.doi.org/10.1073/pnas.2206333119 |
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author | McMahon, Meagan O’Dell, George Tan, Jessica Sárközy, András Vadovics, Máté Carreño, Juan Manuel Puente-Massaguer, Eduard Muramatsu, Hiromi Bajusz, Csaba Rijnink, Willemijn Beattie, Mitchell Tam, Ying K. Kirkpatrick Roubidoux, Ericka Francisco, Isabel Strohmeier, Shirin Kanekiyo, Masaru Graham, Barney S. Krammer, Florian Pardi, Norbert |
author_facet | McMahon, Meagan O’Dell, George Tan, Jessica Sárközy, András Vadovics, Máté Carreño, Juan Manuel Puente-Massaguer, Eduard Muramatsu, Hiromi Bajusz, Csaba Rijnink, Willemijn Beattie, Mitchell Tam, Ying K. Kirkpatrick Roubidoux, Ericka Francisco, Isabel Strohmeier, Shirin Kanekiyo, Masaru Graham, Barney S. Krammer, Florian Pardi, Norbert |
author_sort | McMahon, Meagan |
collection | PubMed |
description | Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses. |
format | Online Article Text |
id | pubmed-9659346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-96593462023-05-02 Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses McMahon, Meagan O’Dell, George Tan, Jessica Sárközy, András Vadovics, Máté Carreño, Juan Manuel Puente-Massaguer, Eduard Muramatsu, Hiromi Bajusz, Csaba Rijnink, Willemijn Beattie, Mitchell Tam, Ying K. Kirkpatrick Roubidoux, Ericka Francisco, Isabel Strohmeier, Shirin Kanekiyo, Masaru Graham, Barney S. Krammer, Florian Pardi, Norbert Proc Natl Acad Sci U S A Biological Sciences Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses. National Academy of Sciences 2022-11-02 2022-11-08 /pmc/articles/PMC9659346/ /pubmed/36322769 http://dx.doi.org/10.1073/pnas.2206333119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences McMahon, Meagan O’Dell, George Tan, Jessica Sárközy, András Vadovics, Máté Carreño, Juan Manuel Puente-Massaguer, Eduard Muramatsu, Hiromi Bajusz, Csaba Rijnink, Willemijn Beattie, Mitchell Tam, Ying K. Kirkpatrick Roubidoux, Ericka Francisco, Isabel Strohmeier, Shirin Kanekiyo, Masaru Graham, Barney S. Krammer, Florian Pardi, Norbert Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title | Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title_full | Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title_fullStr | Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title_full_unstemmed | Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title_short | Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses |
title_sort | assessment of a quadrivalent nucleoside-modified mrna vaccine that protects against group 2 influenza viruses |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659346/ https://www.ncbi.nlm.nih.gov/pubmed/36322769 http://dx.doi.org/10.1073/pnas.2206333119 |
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