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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
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.
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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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