Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Norbert Pardi, Kaela Parkhouse, Ericka Kirkpatrick, Meagan McMahon, Seth J. Zost, Barbara L. Mui, Ying K. Tam, Katalin Karikó, Christopher J. Barbosa, Thomas D. Madden, Michael J. Hope, Florian Krammer, Scott E. Hensley () and Drew Weissman ()
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Norbert Pardi: University of Pennsylvania
Kaela Parkhouse: University of Pennsylvania
Ericka Kirkpatrick: Icahn School of Medicine at Mount Sinai
Meagan McMahon: Icahn School of Medicine at Mount Sinai
Seth J. Zost: University of Pennsylvania
Barbara L. Mui: Acuitas Therapeutics
Ying K. Tam: Acuitas Therapeutics
Katalin Karikó: BioNTech RNA Pharmaceuticals
Christopher J. Barbosa: Acuitas Therapeutics
Thomas D. Madden: Acuitas Therapeutics
Michael J. Hope: Acuitas Therapeutics
Florian Krammer: Icahn School of Medicine at Mount Sinai
Scott E. Hensley: University of Pennsylvania
Drew Weissman: University of Pennsylvania

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

Date: 2018
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DOI: 10.1038/s41467-018-05482-0

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