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

Nat Commun. 2018 Aug 22;9(1):3361. doi: 10.1038/s41467-018-05482-0.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Cells, Cultured
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ferrets
  • Flow Cytometry
  • Hemagglutinins / immunology*
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae / immunology*
  • Phylogeny
  • RNA, Messenger / chemistry*
  • RNA, Messenger / immunology*
  • Rabbits


  • Antibodies, Viral
  • Hemagglutinins
  • RNA, Messenger