Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses

Norbert Pardi; Juan Manuel Carreño; George O’Dell; Jessica Tan; Csaba Bajusz; Hiromi Muramatsu; Willemijn Rijnink; Shirin Strohmeier; Madhumathi Loganathan; Dominika Bielak; Molly M.H. Sung; Ying K. Tam; Florian Krammer; Meagan McMahon

doi:10.1038/s41467-022-32149-8

Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses

Norbert Pardi, Juan Manuel Carreño, George O’Dell, Jessica Tan, Csaba Bajusz, Hiromi Muramatsu, Willemijn Rijnink, Shirin Strohmeier, Madhumathi Loganathan, Dominika Bielak, Molly M.H. Sung, Ying K. Tam, Florian Krammer, Meagan McMahon

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60 Scopus citations

Abstract

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

Original language	English
Article number	4677
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32149-8
State	Published - Dec 2022

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Pardi, N., Carreño, J. M., O’Dell, G., Tan, J., Bajusz, C., Muramatsu, H., Rijnink, W., Strohmeier, S., Loganathan, M., Bielak, D., Sung, M. M. H., Tam, Y. K., Krammer, F., & McMahon, M. (2022). Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses. Nature Communications, 13(1), Article 4677. https://doi.org/10.1038/s41467-022-32149-8

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title = "Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses",

abstract = "Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.",

author = "Norbert Pardi and Carre{\~n}o, {Juan Manuel} and George O{\textquoteright}Dell and Jessica Tan and Csaba Bajusz and Hiromi Muramatsu and Willemijn Rijnink and Shirin Strohmeier and Madhumathi Loganathan and Dominika Bielak and Sung, {Molly M.H.} and Tam, {Ying K.} and Florian Krammer and Meagan McMahon",

note = "Publisher Copyright: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

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Pardi, N, Carreño, JM, O’Dell, G, Tan, J, Bajusz, C, Muramatsu, H, Rijnink, W, Strohmeier, S, Loganathan, M, Bielak, D, Sung, MMH, Tam, YK, Krammer, F & McMahon, M 2022, 'Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses', Nature Communications, vol. 13, no. 1, 4677. https://doi.org/10.1038/s41467-022-32149-8

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AU - Muramatsu, Hiromi

AU - Rijnink, Willemijn

AU - Strohmeier, Shirin

AU - Loganathan, Madhumathi

AU - Bielak, Dominika

AU - Sung, Molly M.H.

AU - Tam, Ying K.

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AU - McMahon, Meagan

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AB - Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

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Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses

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