Human antibodies binding to RSV G protein
The disclosure relates to isolated antibodies and antigen-binding fragments that bind to the G protein of RSV and which are capable of neutralizing RSV A and B subtypes, and the use thereof in the diagnosis, prophylaxis, and/or treatment of RSV infections.
1. An isotonic parenteral composition comprising
an antibody able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antibody is selected from the group consisting of:
a) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:1, a heavy chain CDR2 region of SEQ ID NO:2, and 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,
b) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:4, a heavy chain CDR2 region of SEQ ID NO:5, and a heavy chain CDR3 region of SEQ ID NO:6, a light chain CDR1 region of SEQ ID NO:16, a light chain CDR2 region of SEQ ID NO:17, and a light chain CDR3 region of SEQ ID NO:18,
c) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:7, a heavy chain CDR2 region of SEQ ID NO:8, and a heavy chain CDR3 region of SEQ ID NO:9, a light chain CDR1 region of SEQ ID NO:19, a light chain CDR2 region of SEQ ID NO:20, and a light chain CDR3 region of SEQ ID NO: 21,
d) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:10, a heavy chain CDR2 region of SEQ ID NO:11, and a heavy chain CDR3 region of SEQ ID NO:12, a light chain CDR1 region of SEQ ID NO:22, a light chain CDR2 region of SEQ ID NO:23, and a light chain CDR3 region of SEQ ID NO:24,
e) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:25, a heavy chain CDR2 region of SEQ ID NO:26, and a heavy chain CDR3 region of SEQ ID NO:27, a light chain CDR1 region of SEQ ID NO:28, a light chain CDR2 region of SEQ ID NO:29, and a light chain CDR3 region of SEQ ID NO:30; and
f) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:31, a heavy chain CDR2 region of SEQ ID NO:32, and a heavy chain CDR3 region of SEQ ID NO:33, a light chain CDR1 region of SEQ ID NO:34, a light chain CDR2 region of SEQ ID NO:35, and a light chain CDR3 region of SEQ ID NO:36; and
at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of a buffer, an antioxidant, and mixtures thereof; and
wherein the composition comprises at least one therapeutic agent and/or detectable agent bonded thereto; or wherein the antibody is lyophilized.
2. The antibody of claim 1 , wherein the antibody is a human antibody.
3. An isotonic parenteral composition comprising
an antigen-binding fragment able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antigen-binding fragment binds to an epitope within the central conserved domain of the RSV G protein, wherein the antigen-binding fragment comprises a heavy chain CDR1 region of SEQ ID NO:1, a heavy chain CDR2 region of SEQ ID NO:2, and 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; and
at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of a buffer, an antioxidant, and mixtures thereof; and
wherein the antigen-binding fragment further comprises at least one therapeutic agent and/or detectable agent bonded thereto; or wherein the antigen-binding fragment is lyophilized.
4. An isotonic parenteral composition comprising
a functional variant of an antibody that is able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the functional variant binds to an epitope within the central conserved domain of the RSV G protein, wherein the functional variant comprises a heavy chain CDR1 region of SEQ ID NO:1, a heavy chain CDR2 region of SEQ ID NO:2, and 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; and
at least one pharmaceutically acceptable excipient, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of a buffer, an antioxidant, and mixtures thereof; and
wherein the functional variant further comprises at least one therapeutic agent and/or detectable agent bonded thereto; or wherein the functional variant is lyophilized.
5. A method of inhibiting RSV in a subject, the method comprising:
administering to the subject a therapeutically effective amount of the antibody of claim 2 .
6. A kit comprising the isotonic parenteral composition according to claim 1 .
7. A method of detecting RSV infection, the method comprising:
assaying the level of RSV antigen in a sample using the antibody of claim 2 ; and
comparing the assayed level of RSV antigen with a control level,
wherein an increase in the assayed level of RSV antigen compared to the control level is indicative of RSV infection.
8. A method of detecting RSV infection, the method comprising:
assaying the level of RSV antigen in a sample with the functional variant of claim 6 , and comparing the assayed level of RSV antigen with a control level,
wherein an increase in the assayed level of RSV antigen compared to the control level is indicative of RSV infection.