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 () and Meagan McMahon ()
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Norbert Pardi: University of Pennsylvania
Juan Manuel Carreño: Icahn School of Medicine at Mount Sinai
George O’Dell: Icahn School of Medicine at Mount Sinai
Jessica Tan: Icahn School of Medicine at Mount Sinai
Csaba Bajusz: University of Pennsylvania
Hiromi Muramatsu: University of Pennsylvania
Willemijn Rijnink: Icahn School of Medicine at Mount Sinai
Shirin Strohmeier: Icahn School of Medicine at Mount Sinai
Madhumathi Loganathan: Icahn School of Medicine at Mount Sinai
Dominika Bielak: Icahn School of Medicine at Mount Sinai
Molly M. H. Sung: Acuitas Therapeutics
Ying K. Tam: Acuitas Therapeutics
Florian Krammer: Icahn School of Medicine at Mount Sinai
Meagan McMahon: Icahn School of Medicine at Mount Sinai

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32149-8

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