Influenza virus vaccines and uses thereof

A polypeptide comprising:

• (A) (a) (i) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment, or a deleted form of said HA1 N-terminal stem segment, wherein up to 7, 6, 5, 4, 3, 2, or 1 amino acid residues are deleted, covalently linked to (ii) a linker of 1 to 50 heterologous residues that is in turn covalently linked to (iii) an HA1 C-terminal short stem segment, or a deleted form of said HA1 C-terminal short stem segment, wherein up to 7, 6, 5, 4, 3, 2, or 1 amino acid residues are deleted;
• said HA1 domain being in tertiary association with
• (b) an influenza hemagglutinin HA2 domain, wherein the amino acid sequence of the HA2 domain is at least 70%, 75%, 80%, 85%, 90%, 95%, 96% or 98% identical to the amino acid sequence of an HA2 from an H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16 influenza A,
• wherein the HA1 N-terminal stem segment consists of amino acid residues HA1N-term through Ap of the HA1 domain, wherein HA1N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide, and wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering;
• and
• wherein the HA1 C-terminal short stem segment consists of amino acid residues Bq through HA1C-term of an HA1 domain, wherein Bq is Cys that corresponds to amino acid position 305 of an HA1 domain using H3 numbering, and wherein HA1C-term is the C-terminal amino acid of the HA1 domain;
• or
• (B) (a) (i) an influenza hemagglutinin HA1 domain that comprises a deleted form of an HA1 N-terminal stem segment, wherein up to 7, 6, 5, 4, 3, 2, or 1 amino acid residues are deleted, covalently linked to (ii) a linker of 1 to 50 heterologous residues that is in turn covalently linked to (iii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96% or 98% amino acid sequence identity to an HA1 C-terminal short stem segment from an H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16 influenza A;
• said HA1 domain being in tertiary association with
• (b) an influenza hemagglutinin HA2 domain, wherein the amino acid sequence of the HA2 domain is at least 70%, 75%, 80%, 85%, 90%, 95%, 96% or 98% identical to the amino acid sequence of an HA2 from an H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16 influenza A,
• wherein the HA1 N-terminal stem segment consists of amino acid residues HA1N-term through Ap of the HA1 domain, wherein HA1N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide, and wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering;
• and
• wherein the HA1 C-terminal short stem segment consists of amino acid residues Bq through HA1C-term of an HA1 domain, wherein Bq is Cys that corresponds to amino acid position 305 of an HA1 domain using H3 numbering, and wherein HA1C-term is the C-terminal amino acid of the HA1 domain.