Influenza mRNA vaccines

A method for stimulating an anti-influenza immune response in a subject comprising administering to the subject an effective amount of a composition comprising:

• (i) at least three mRNAs encoding three different influenza virus hemagglutinin (HA) proteins, or antigenic fragments thereof, wherein said at least three mRNAs encode an HA from influenza B, an HA1 from influenza A, and an HA3 from influenza A;
• and
• (ii) at least three mRNAs encoding three different influenza neuraminidase (NA) proteins, or antigenic fragments thereof, wherein at least one of said at least three mRNAs encodes a NA from influenza B,
• wherein each of the mRNAs is formulated with a lipid nanoparticle (LNP) comprising a cationic lipid,
• wherein each of said mRNAs comprises a coding sequence encoding the HA or NA protein that has a G/C content that is increased compared to the G/C content of the corresponding coding sequence of a wild type mRNA encoding the HA or NA protein, and
• wherein each of said mRNAs comprises:
• (a) a m7GpppN 5′-CAP structure;
• (b) a 5′-UTR element;
• (c) a 3′-UTR element comprising a histone stem loop element having the RNA sequence of SEQ ID NO:
• 213735;
• and (d) a poly(A) sequence comprising 60 to 250 consecutive adenosines,
• thereby stimulating an anti-influenza immune response in a subject, wherein the composition is administered by intramuscular or intradermal injection.