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Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies
Nature Communicationsvolume 9, Article number: 3361 (2018) | Download Citation
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.
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- Norbert Pardi,
- Kaela Parkhouse,
- Ericka Kirkpatrick,
- Meagan McMahon,
- Seth J. Zost,
- Barbara L. Mui,
- Ying K. Tam,
- Katalin Karik?,
- Christopher J. Barbosa,
- Thomas D. Madden,
- Michael J. Hope,
- Florian Krammer,
- Scott E. Hensley &
- Drew Weissman
Nature Communicationsvolume 9, Article number: 3361 (2018) | Download Citation
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.
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