Filovirus antibody
The present invention addresses a need for antibodies useful for filovirus infections.
1. An isolated humanized anti-filovirus anti-Sudan strain Ebola virus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region, and comprising:
(a) a heavy chain CDR1 comprising GFAFNYYDMF (SEQ ID NO:1); a heavy chain CDR2 comprising YIKPGGGNTYYADSV (SEQ ID NO:2); and a heavy chain CDR3 comprising QLYGNSFFDY (SEQ ID NO:3); and
(b) a light chain sequence CDR1 comprising DVTTA (SEQ ID NO:4); a light chain sequence CDR2 comprising WASTR (SEQ ID NO:5); and a light chain sequence CDR3 comprising HYSTPLT (SEQ ID NO:6).
2. The humanized antibody of claim 1 , wherein the light chain comprises the sequence:
(SEQ ID NO: 7)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW
ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ
GTKVEIK.
3. The humanized antibody of claim 1 , wherein the light chain comprises the sequence:
(SEQ ID NO: 8)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKWYWAS
TRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGT
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGECGGS
or
(SEQ ID NO: 13)
DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKWYWAS
TRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGT
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC.
4. The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence:
(SEQ ID NO: 9)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY
IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL
YGNSFFDYWGQGTLVTVSS.
5. The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence:
(SEQ ID NO: 10)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAYI
KPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYG
NSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS
VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK,
(SEQ ID NO: 11)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAYI
KPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYG
NSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS
VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG,
or
(SEQ ID NO: 12)
EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAYI
KPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYG
NSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS
VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.
6. An antigen-binding fragment of the antibody of claim 1 .
7. A recombinant nucleic acid encoding the antibody of claim 1 .
8. A cell, wherein the cell is not in a human subject, transformed with the recombinant nucleic acid of claim 7 .
9. A composition comprising the antibody of claim 1 or an antigen binding fragment thereof.
10. The composition of claim 9 , comprising a pharmaceutically acceptably carrier.
11. A method of treating a filovirus infection in a subject comprising administering to the subject an amount of the antibody of claim 1 or an antigen-binding fragment thereof effective to treat a filovirus infection in a subject, wherein the filovirus is a Sudan strain Ebola virus.
12. The method of claim 11 , wherein the antibody or the antigen-binding fragment is administered after the subject has been exposed to the filovirus.
13. A method of inhibiting a filovirus infection of a subject comprising administering to the subject an amount of the antibody of claim 1 or an antigen-binding fragment thereof effective to inhibit a filovirus infection in a subject, wherein the filovirus is a Sudan strain Ebola virus.
14. The method of claim 13 , wherein the antibody or the antigen-binding fragment is administered prior to the subject being exposed to the filovirus.
15. The antibody of claim 1 or an antigen-binding fragment thereof, wherein the antibody is a neutralizing antibody.