Neutralizing molecules to viral antigens
The present invention concerns methods and means for identifying, producing, and engineering neutralizing molecules against influenza A viruses, and to the neutralizing molecules produced. In particular, the invention concerns neutralizing molecules against various influenza A virus subtypes, including neutralizing antibodies against H5 and/or H3 and/or H1, such as, for example all of H1, H3, and H5 subtypes, and methods and means for making such molecules.
1. A composition comprising an antibody, or an antigen binding fragment thereof, comprising a heavy chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:9, SEQ ID NO:45 and SEQ ID NO:61, wherein the antibody:
(i) neutralizes more than one subtype and/or more than one isolate of an influenza A virus,
(ii) binds to a hemagglutinin (HA) stem polypeptide or fragment thereof that lacks an HA globular head polypeptide, and
(iii) does not inhibit hemagglutination.
2. The composition of claim 1 , effective against at least one additional influenza A virus subtype selected from the group consisting of H1, H2, H3, H5, H6, H7, H8, and H9.
3. The composition of claim 1 , effective against at least two isolates of an influenza A virus subtype selected from the group consisting of H1, H2, H3, H5, H6, H7, H8, and H9.
4. The composition of claim 1 , effective against at least one isolate of H1 influenza A virus subtype.
5. The composition of claim 1 , effective against at least one isolate of H5 influenza A virus subtype.
6. The composition of claim 1 , effective against isolates of H1 and H5 influenza A virus subtypes.
7. The composition of claim 1 , wherein the antibody or antigen binding fragment thereof further comprises a light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:71, SEQ ID NO:81, SEQ ID NO:140, SEQ ID NO:158, SEQ ID NO:159, and SEQ ID NO:160.
8. The composition of claim 1 , wherein at least one of said virus subtypes has the ability to infect humans.
9. The composition of claim 1 , wherein at least one of said isolates has been obtained from a human subject.
10. The composition of claim 1 , wherein at least one of said isolates has been obtained from a non-human animal.
11. The composition of claim 1 , wherein the composition further contains an attenuated influenza A virus or a killed influenza A virus.