Binding molecules directed against influenza hemagglutinin and uses thereof
Multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains comprising HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.
1. An isolated polypeptide comprising a single domain antibody and an Fc region, wherein the single domain antibody is capable of binding specifically to an HA of a first influenza strain and has an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 20, 24, 25, 155, 176, 197, and 203.
2. The isolated polypeptide of claim 1 , wherein the single domain antibody binds to an epitope in the stem region of HA.
3. The isolated polypeptide of claim 1 , wherein the single domain antibody binds to an epitope in the head region of influenza B HA.
4. The isolated polypeptide of claim 1 , wherein the single domain antibody has the amino acid sequence of SEQ ID NO: 155, 176, 197, or 203.
5. The isolated polypeptide according to claim 1 , wherein the Fc region is a human IgG Fc region.
6. The isolated polypeptide according to claim 1 , further comprising a region that that is capable of binding to an HA of a second influenza strain.
7. The isolated polypeptide of claim 6 , wherein the first influenza strain is an influenza A strain and the second influenza strain is an influenza B strain.
8. An isolated antibody comprising the polypeptide of claim 1 .
9. An isolated antibody comprising the polypeptide of claim 7 .
10. An isolated nucleic acid encoding the polypeptide of claim 1 .
11. An isolated nucleic acid encoding the polypeptide of claim 7 .
12. A vector comprising the isolated nucleic acid of claim 10 .
13. A vector comprising the isolated nucleic acid of claim 11 .
14. A pharmaceutical composition comprising the isolated polypeptide of claim 1 .
15. A pharmaceutical composition comprising the isolated polypeptide of claim 7 .
16. A pharmaceutical composition comprising the isolated nucleic acid of claim 10 .
17. A pharmaceutical composition comprising the isolated nucleic acid of claim 11 .