Anti-respiratory syncytial virus antibodies, and methods of their generation and use
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as nucleic acid sequences encoding such antibodies, methods for their identification, isolation, generation, and methods for their preparation and use are provided.
1. An isolated antibody or antigen-binding fragment thereof that binds to Respiratory Syncytial Virus (RSV) F protein (F), which comprises a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3; and a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOS: 163, 165, 167, 171, 173 and 175 respectively.
2. The antibody or antibody fragment according to claim 1 , wherein:
the VH comprises an amino acid sequence that possesses at least 90% sequence identity to SEQ ID NO: 162; and/or
the VL comprises an amino acid sequence that possesses at least 90% sequence identity to SEQ ID NO: 170.
3. The antibody or antibody fragment according to claim 1 , wherein:
the VH comprises an amino acid sequence that possesses at least 95% sequence identity to SEQ ID NO: 162; and/or
the VL comprises an amino acid sequence that possesses at least 95% sequence identity to SEQ ID NO: 170.
4. The antibody or antibody fragment according to claim 1 , wherein:
the VH comprises the amino acid sequence of SEQ ID NO: 162; and/or the VL comprises the amino acid sequence of SEQ ID NO: 170.
5. The antibody or antibody fragment according to claim 1 , wherein:
the VH consists of the amino acid sequence of SEQ ID NO: 162; and
(B) the VL consists of the amino acid sequence of SEQ ID NO: 170.
6. A pharmaceutical composition comprising: (i) the antibody or antibody fragment according claim 1 ; and (ii) a pharmaceutically acceptable carrier and/or excipient.
7. A pharmaceutical composition comprising: (i) antibody or antibody fragment according claim 2 ; and (ii) a pharmaceutically acceptable carrier and/or excipient.
8. A pharmaceutical composition comprising: (i) the antibody or antibody fragment according claim 3 ; and (ii) a pharmaceutically acceptable carrier and/or excipient.
9. A pharmaceutical composition comprising: (i) the antibody or antibody fragment according claim 4 ; and (ii) a pharmaceutically acceptable carrier and/or excipient.
10. A pharmaceutical composition comprising: (i) the antibody or antibody fragment according claim 5 ; and (ii) a pharmaceutically acceptable carrier and/or excipient.
11. An isolated or recombinant nucleic acid encoding an antibody or antibody fragment according to claim 1 or a vector comprising said nucleic acid.
12. An isolated or recombinant nucleic acid encoding an antibody or antibody fragment according to claim 2 or a vector comprising said nucleic acid.
13. An isolated or recombinant nucleic acid encoding an antibody or antibody fragment according to claim 3 or a vector comprising said nucleic acid.
14. An isolated or recombinant nucleic acid encoding an antibody or antibody fragment according to claim 4 or a vector comprising said nucleic acid.
15. An isolated or recombinant nucleic acid encoding an antibody or antibody fragment according to claim 5 or a vector comprising said nucleic acid.
16. A host cell transfected, transformed, or transduced with the isolated or recombinant nucleic acid according to claim 11 or an expression vector containing said nucleic acid.
17. A host cell transfected, transformed, or transduced with the isolated or recombinant nucleic acid according to claim 12 or an expression vector containing said nucleic acid.
18. A host cell transfected, transformed, or transduced with the isolated or recombinant nucleic acid according to claim 13 or an expression vector containing said nucleic acid.
19. A host cell transfected, transformed, or transduced with the isolated or recombinant nucleic acid according to claim 14 or an expression vector containing said nucleic acid.
20. A host cell transfected, transformed, or transduced with the isolated or recombinant nucleic acid according to claim 15 or an expression vector containing said nucleic acid.
21. A method of treating or preventing RSV infection and/or HMPV infection, or at least one symptom associated with RSV infection and/or HMPV infection, comprising administering to a patient in need thereof or suspected of being in need thereof one or more antibodies or antigen-binding fragments thereof that bind to Respiratory Syncytial Virus (RSV) F protein (F), and which neutralize hMPV, wherein said one or more antibodies or antigen-binding fragments thereof (i) comprise a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3; and (ii) a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOS: 163, 165, 167, 171, 173 and 175 respectively, such that the RSV infection and/or the HMPV infection is treated or prevented, or the at least one symptom associated with RSV infection is treated, alleviated, or reduced in severity.
22. The method of claim 21 , wherein the one or more antibodies or antigen-binding fragments thereof (i) comprise a VH region comprising the amino acid sequence of SEQ ID NO: 162; and (ii) a VL region comprising the amino acid sequence of SEQ ID NO: 170.