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. A single domain antibody (sdAb) comprising one of the amino acid sequences selected from the group consisting of SEQ ID NO: 155, SEQ ID NO: 176, SEQ ID NO: 197, and SEQ ID NO: 203.
2. A multi-domain antibody comprising at least two of the sdAbs of claim 1 .
3. The multi-domain antibody of claim 2 , comprising four sdAbs having the amino acid sequence of SEQ ID NO: 155, the amino acid sequence of SEQ ID NO: 176, the amino acid sequence of SEQ ID NO: 197, and the amino acid sequence of SEQ ID NO: 203, respectively.
4. A multi-domain antibody comprising a first polypeptide comprising a first single domain antibody (sdAb) comprising the amino acid sequence of SEQ ID NO: 155 fused to a second sdAb comprising the amino acid sequence of SEQ ID NO: 176; and a second polypeptide comprising a third sdAb comprising the amino acid sequence of SEQ ID NO: 197 fused to a fourth sdAb comprising the amino acid sequence of SEQ ID NO: 203.
5. The multi-domain antibody of claim 4 , wherein the first sdAb is fused to the second sdAb via a linker; and the third sdAb is fused to the fourth sdAb via a linker.
6. The multi-domain antibody of claim 4 , wherein at least one of the first polypeptide and the second polypeptide further comprises a human Fc tail.
7. The multi-domain antibody of claim 6 , wherein each of the first polypeptide and second polypeptide independently further comprises a human Fc tail.
8. A multi-domain antibody comprising a first polypeptide chain comprising, from N-terminus to C-terminus, a first single domain antibody (sdAb) comprising the amino acid sequence of SEQ ID NO: 176 fused to a second sdAb comprising the amino acid sequence of SEQ ID NO: 155 via a linker comprising the amino acid sequence of SEQ ID NO: 142; and a second polypeptide chain comprising, from N-terminus to C-terminus, a third sdAb comprising the amino acid sequence of SEQ ID NO: 203 fused to a fourth sdAb comprising the amino acid sequence of SEQ ID NO: 197 via a linker comprising the amino acid sequence of SEQ ID NO: 142.
9. The multi-domain antibody of claim 8 , wherein each of the first polypeptide and second polypeptide independently further comprises a human Fc tail.
10. A multi-domain antibody comprising a first polypeptide chain having the amino acid sequence of SEQ ID NO: 320 and a second polypeptide chain having the amino acid sequence of SEQ ID NO: 321.
11. A pharmaceutical composition comprising the sdAb antibody of claim 1 .
12. A pharmaceutical composition comprising the multi-domain antibody of claim 4 .
13. A pharmaceutical composition comprising the multi-domain antibody of claim 8 .
14. A pharmaceutical composition comprising the multi-domain antibody of claim 10 .
15. A method of inhibiting an influenza infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 11 .
16. A method of inhibiting an influenza infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 12 .
17. A method of inhibiting an influenza infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 13 .
18. A method of inhibiting an influenza infection in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 14 .
19. A nucleic acid molecule encoding the single domain antibody of claim 1 .
20. A nucleic acid molecule encoding the multi-domain antibody of claim 4 .
21. A nucleic acid molecule encoding the multi-domain antibody of claim 8 .
22. A nucleic acid molecule encoding the multi-domain antibody of claim 10 .