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, Drew Weissman

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

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.

Original languageEnglish
Article number3361
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

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