Human binding molecules capable of neutralizing influenza virus H5N1 and uses thereof
Described are binding molecules such as human monoclonal antibodies that bind to influenza virus H5N1 and have neutralizing activity against influenza virus H5N1. Also described are nucleic acid molecules encoding the antibodies, and compositions comprising the antibodies and methods of identifying or producing the antibodies. The antibodies can be used in the diagnosis, prophylaxis, and/or treatment of an influenza virus H5N1 infection. In certain embodiments, the antibodies provide cross-subtype protection in vivo, such that infections with H5, H2, H6, H9, and H1-based influenza subtypes can be prevented and/or treated.
1. An isolated binding molecule able to recognize and bind to an epitope in the HA2 subunit of the influenza hemagglutinin protein (HA), wherein the binding molecule has neutralizing activity against an influenza virus comprising HA of the H5 subtype, wherein the binding molecule comprises a heavy chain CDR1 region of SEQ ID NO: 1, a heavy chain CDR2 region of SEQ ID NO: 2, a heavy chain CDR3 region of SEQ ID NO: 3, a light chain CDR1 region of SEQ ID NO: 13, a light chain CDR2 region of SEQ ID NO: 14, and a light chain CDR3 region of SEQ ID NO: 15.
2. The binding molecule of claim 1 , which also has neutralizing activity against an influenza virus comprising HA of the HI subtype.
3. The isolated binding molecule of claim 1 , wherein the H5 subtype is selected from the group consisting of H5N1, H5N2, H5N8, and H5N9.
4. The binding molecule of claim 2 , wherein the HI subtype is H1N1.
5. The binding molecule of claim 1 , wherein the binding molecule is a human monoclonal antibody.
6. A method of producing a binding molecule, the method comprising:
expressing a nucleic acid molecule encoding the binding molecule of claim 1 in a host cell.
7. A composition comprising:
the binding molecule of claim 1 , and a pharmaceutically acceptable excipient.
8. The method of claim 6 , further comprising:
inserting the nucleic acid molecule into a vector.
9. The method of claim 8 , further comprising:
culturing a host cell comprising the said vector.
10. The method of claim 9 , further comprising:
culturing the host cell under conditions so as to express the binding molecule.
11. The method of claim 10 , further comprising:
recovering the expressed binding molecule.
12. A vector comprising a nucleic acid molecule, wherein the nucleic acid molecule encodes the binding molecule of claim 1 , wherein the vector is selected from the group consisting of plasmids, cosmids, bacterial artificial chromosomes (BAC), yeast artificial chromosomes (YAC) and vectors derived from bacteriophages or plant or animal viruses.