Therapy for filovirus infection
The present invention addresses a need for improved treatments for filovirus infections. This invention provides an isolated humanized anti-filovirus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region. Also provided is a method of treating and/or inhibiting a filovirus infection in a subject comprising administering to the subject an amount of any of the antibodies described herein, or an amount of an antigen-binding fragment thereof. Also provided is composition comprising any of the antibodies described herein, or or an amount of an antigen-binding fragment thereof. In an embodiment, the composition comprises a pharmaceutically acceptably carrier.
1. An isolated humanized 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 CDR3 comprising QLYGNSFFDY (SEQ ID NO:4), a heavy chain CDR1 comprising GFAFNYYDMF (SEQ ID NO:17), and a heavy chain CDR2 comprising YIKPGGGNTYYADSV (SEQ ID NO:2),
and
(b) a light chain sequence, comprising a light chain CDR1, CDR2 and CDR3, wherein the light chain CDR3 comprises CQQHYSTPLT (residues 88-97 of SEQ ID NO:39), and comprising DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKL (SEQ ID NO:12) which contains the light chain CDR1, and LIYAASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ (SEQ ID NO:15) which contains the light chain CDR2.
2. The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence WVAYIKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTA (SEQ ID NO:9).
3. The humanized antibody of claim 1 , wherein the heavy chain comprises the sequence VYYCARQLYGNSFFDYWGQGTLVTV (SEQ ID NO:11).
4. The humanized antibody of claim 1 , wherein the light chain comprises the sequence DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKL (SEQ ID NO:12).
5. The humanized antibody of claim 1 , wherein the light chain comprises the sequence HYSTPLTFGQGTKVFI (SEQ ID NO:16).
6. An antigen-binding fragment of the antibody of claim 1 .
7. A composition comprising the antibody of claim 1 or the antigen-binding fragment of claim 6 .
8. The composition of claim 7 , comprising a pharmaceutically acceptable carrier.
9. A method of treating a filovirus infection in a subject comprising administering to the subject an amount of the antibody of claim 1 or the antigen-binding fragment of claim 6 effective to treat a filovirus infection in a subject wherein the filovirus is a Sudan strain Ebola virus.
10. The method of claim 9 , wherein the antibody or antigen-binding fragment are administered after the subject has been exposed to the filovirus.
11. A method of inhibiting a filovirus infection of a subject comprising administering to the subject an amount of the antibody of claim 1 or the antigen-binding fragment of claim 6 effective to inhibit 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 antigen-binding fragment are administered prior to the subject being exposed to the filovirus.
13. The antibody of claim 1 or the antigen-binding fragment of claim 6 , wherein the antibody is a neutralizing antibody.
14. A method of treating a filovirus infection in a subject comprising administering to the subject an amount of the composition of claim 7 effective to treat a filovirus infection in a subject, wherein the filovirus is a Sudan strain Ebola virus.
15. A method of inhibiting a filovirus infection of a subject comprising administering to the subject an amount of the composition of claim 7 effective to inhibit a filovirus infection in a subject, wherein the filovirus is a Sudan strain Ebola virus.