Influenza vaccine

1. A method of inducing an influenza virus antigen-specific immune response in a human subject, the method comprising administering to the human subject a composition comprising 10-100 μg of a messenger ribonucleic acid (mRNA) polynucleotide to thereby induce a protective antigen-specific immune response in the subject, wherein the mRNA polynucleotide comprises an open reading frame encoding an influenza virus hemagglutinin (HA) antigen and is formulated in a lipid nanoparticle (LNP), wherein 100% of uracil nucleosides in the open reading frame are N1-methylpseudouridine, and wherein the LNP comprises a compound of Formula (I):

or a salt thereof, wherein:

R 1 is selected from the group consisting of C 5-30 alkyl, C 5-20 alkenyl, and —R″M′R′;

R 2 and R 3 are independently selected from the group consisting of C 1-14 alkyl and C 2-14 alkenyl;

R 4 is —(CH 2 ) n Q, where Q is —OR, and each n is independently selected from 1, 2, 3, 4, and 5;

each R 5 is H;

each R 6 is H;

M and M′ are independently selected from —C(O)O—

and —OC(O)—;

R 7 is H;

R is H;

R′ is H;

R″ is selected from the group consisting of C 3-14 alkyl and C 3-14 alkenyl; and

m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.

2. The method of claim 1 , wherein the compound of Formula (I) is Compound 25:

3. The method of claim 1 , wherein the LNP comprises 20-60 mol % cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid, wherein the LNP comprises 0.5 mol % to 5 mol % PEG-modified lipid.

4. The method of claim 1 , wherein the HA antigen is an H10 HA antigen.

5. The method of claim 4 , wherein the H10 HA antigen comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 4.

6. The method of claim 4 , wherein the HA antigen is an H10N8 HA antigen.

7. The method of claim 1 , wherein the antigen-specific immune response comprises a B cell response.

8. The method of claim 1 , wherein the antigen-specific immune response comprises a T cell response.

9. The method of claim 1 , further comprising administering a booster dose of the composition to the human subject.

10. The method of claim 1 , wherein the method of producing an antigen-specific immune response involves a single administration of the composition, and wherein the protective immune response is produced with the single administration.