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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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Detalles Bibliográficos
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
Descripción
Sumario: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.