Rabies virus G protein epitope, and rabies virus neutralising binding molecule that binds specifically thereto
This invention relates to a rabies virus G protein epitope and a rabies-virus-neutralizing binding molecule that binds specifically thereto, wherein different epitope sites of rabies virus G protein are identified and binding molecules that bind thereto and a cocktail thereof can be found to retain neutralizing activity against various rabies viruses.
1. A rabies-virus-neutralizing antibody which binds to an epitope located between amino acid residues 33 and 215 or an epitope located between amino acid residues 331 and 333 of the wild-type rabies virus G protein, the sequence of which protein is set forth in SEQ ID NO:2,
wherein the antibody comprises:
a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:3, the CDR2 of SEQ ID NO:4, and the CDR3 of SEQ ID NO:5; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:6, the CDR2 of SEQ ID NO:7, and the CDR3 of SEQ ID NO:8; or
a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:9, the CDR2 of SEQ ID NO:10, and the CDR3 of SEQ ID NO:11; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:12, the CDR2 of SEQ ID NO:13, and the CDR3 of SEQ ID NO:14;
or a rabies-virus-neutralizing fragment of such an antibody.
2. The antibody of claim 1 , wherein the binding molecule has a binding affinity (K D ) less than 1×10 −8 M.
3. The antibody of claim 1 , wherein if the antibody comprises a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:3, the CDR2 of SEQ ID NO:4, and the CDR3 of SEQ ID NO:5; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:6, the CDR2 of SEQ ID NO:7, and the CDR3 of SEQ ID NO:8, the heavy chain variable region comprises the sequence set forth in SEQ ID NO:15.
4. The antibody of claim 1 , wherein if the antibody comprises a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:3, the CDR2 of SEQ ID NO:4, and the CDR3 of SEQ ID NO:5; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:6, the CDR2 of SEQ ID NO:7, and the CDR3 of SEQ ID NO:8, the light chain variable region comprises the sequence set forth in SEQ ID NO:16.
5. The antibody of claim 1 , wherein if the antibody comprises a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:9, the CDR2 of SEQ ID NO:10, and the CDR3 of SEQ ID NO:11; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:12, the CDR2 of SEQ ID NO:13, and the CDR3 of SEQ ID NO:14, the heavy chain variable region comprises the sequence set forth in SEQ ID NO:17.
6. The antibody of claim 1 , wherein if the antibody comprises a) a heavy chain variable domain comprising the CDR1 of SEQ ID NO:9, the CDR2 of SEQ ID NO:10, and the CDR3 of SEQ ID NO:11; and b) a light chain variable domain comprising the CDR1 of SEQ ID NO:12, the CDR2 of SEQ ID NO:13, and the CDR3 of SEQ ID NO:14, the light chain variable region comprises the sequence set forth in SEQ ID NO:18.
7. The antibody of claim 3 , wherein the sequence of the heavy chain is set forth in SEQ ID NO:19.
8. The antibody of claim 4 , wherein the sequence of the light chain is set forth in SEQ ID NO:20.
9. The antibody of claim 5 , wherein the sequence of the heavy chain is set forth in SEQ ID NO:21.
10. The antibody of claim 6 , wherein the sequence of the light chain is set forth in SEQ ID NO:22.
11. A composition comprising the antibody of claim 1 and a suitable carrier.
12. The composition of claim 11 , further comprising a second antibody.
13. A method of preventing or treating rabies in a subject which comprises administering to the subject a prophylactically or therapeutically effective amount of the antibody of claim 1 .
14. A method of diagnosing rabies in a subject which comprises contacting a sample from the subject with the antibody of claim 1 under conditions permitting formation of a complex between the antibody and any rabies virus present in the sample and detecting any complex so formed.
15. A package comprising: 1) the composition of claim 11 ; and (2) a package insert providing instructions for use of the composition.