Human antibodies binding to RSV G proteins

1. An antibody able to specifically bind to attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A2 and B strains, wherein the antibody binds to an epitope within the central conserved domain of the RSV G protein, 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:4, a light chain CDR2 region of SEQ ID NO:5, and a light chain CDR3 region of SEQ ID NO:6;

b) 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:10, a heavy chain CDR2 region of SEQ ID NO: 1, and a light chain CDR3 region of SEQ ID NO:12,

c) an antibody comprising a heavy chain CDR1 region of SEQ ID NO: 13, a heavy chain CDR2 region of SEQ ID NO: 14, and a heavy chain CDR3 region of SEQ ID NO:15, 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;

d) an antibody comprising a heavy chain CDR1 region of SEQ ID NO: 19, a heavy chain CDR2 region of SEQ ID NO:20, and a heavy chain CDR3 region of SEQ ID NO:21, 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;

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;

g) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:37, a heavy chain CDR2 region of SEQ ID NO:38, and a heavy chain CDR3 region of SEQ ID NO:39, a light chain CDR1 region of SEQ ID NO:40, a light chain CDR2 region of SEQ ID NO:41, and a light chain CDR3 region of SEQ ID NO:42;

h) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:43, a heavy chain CDR2 region of SEQ ID NO:44, and a heavy chain CDR3 region of SEQ ID NO:45, a light chain CDR1 region of SEQ ID NO:46, a light chain CDR2 region of SEQ ID NO:47, and a light chain CDR3 region of SEQ ID NO:48;

i) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:49, a heavy chain CDR2 region of SEQ ID NO:50 and a heavy chain CDR3 region of SEQ ID NO:51, a light chain CDR1 region of SEQ ID NO:52, a light chain CDR2 region of SEQ ID NO:53, and a light chain CDR3 region of SEQ ID NO:54;

j) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:55, a heavy chain CDR2 region of SEQ ID NO:56, and a heavy chain CDR3 region of SEQ ID NO:57 a light chain CDR1 region of SEQ ID NO:58, a light chain CDR2 region of SEQ ID NO:59, and a light chain CDR3 region of SEQ ID NO:60;

k) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:61, a heavy chain CDR2 region of SEQ ID NO:62, and a heavy chain CDR3 region of SEQ ID NO:63, a light chain CDR1 region of SEQ ID NO:64, a light chain CDR2 region of SEQ ID NO:65, and a light chain CDR3 region of SEQ ID NO:66; and

l) an antibody comprising a heavy chain CDR1 region of SEQ ID NO:67, a heavy chain CDR2 region of SEQ ID NO:68, and a heavy chain CDR3 region of SEQ ID NO:69 a light chain CDR1 region of SEQ ID NO:70, a light chain CDR2 region of SEQ ID NO:71, and a light chain CDR3 region of SEQ ID NO:72.

2. An antigen-binding fragment that specifically binds to the G protein of a respiratory syncytial virus (RSV) and neutralizes RSV A2 and B strains, wherein the antigen-biding fragment is selected from the group consisting of:

a) an antigen-binding fragment 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:4, a light chain CDR2 region of SEQ ID NO:5, and a light chain CDR3 region of SEQ ID NO:6;

b) an antigen-binding fragment 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:10, a heavy chain CDR2 region of SEQ ID NO: 11, and a light chain CDR3 region of SEQ ID NO:12,

c) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:13, a heavy chain CDR2 region of SEQ ID NO: 14, and a heavy chain CDR3 region of SEQ ID NO:15, 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;

d) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:19, a heavy chain CDR2 region of SEQ ID NO:20, and a heavy chain CDR3 region of SEQ ID NO:21, 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 antigen-binding fragment 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;

f) an antigen-binding fragment 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;

g) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:37, a heavy chain CDR2 region of SEQ ID NO:38, and a heavy chain CDR3 region of SEQ ID NO:39, a light chain CDR1 region of SEQ ID NO:40, a light chain CDR2 region of SEQ ID NO:41, and a light chain CDR3 region of SEQ ID NO:42;

h) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:43, a heavy chain CDR2 region of SEQ ID NO:44, and a heavy chain CDR3 region of SEQ ID NO:45, a light chain CDR1 region of SEQ ID NO:46, a light chain CDR2 region of SEQ ID NO:47, and a light chain CDR3 region of SEQ ID NO:48;

i) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:49, a heavy chain CDR2 region of SEQ ID NO:50 and a heavy chain CDR3 region of SEQ ID NO:51, a light chain CDR1 region of SEQ ID NO:52, a light chain CDR2 region of SEQ ID NO:53, and a light chain CDR3 region of SEQ ID NO:54;

j) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:55, a heavy chain CDR2 region of SEQ ID NO:56, and a heavy chain CDR3 region of SEQ ID) NO:57 a light chain CDR1 region of SEQ ID NO:58, a light chain CDR2 region of SEQ ID NO:59, and a light chain CDR3 region of SEQ ID NO:60;

k) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:61, a heavy chain CDR2 region of SEQ ID NO:62, and a heavy chain CDR3 region of SEQ ID NO:63, a light chain CDR1 region of SEQ ID NO:64, a light chain CDR2 region of SEQ ID NO:65, and a light chain CDR3 region of SEQ ID NO:66; and

l) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO:67, a heavy chain CDR2 region of SEQ ID NO:68, and a heavy chain CDR3 region of SEQ ID NO:69 a light chain CDR1 region of SEQ ID NO:70, a light chain CDR2 region of SEQ ID NO:71, and a light chain CDR3 region of SEQ ID NO:72.

3. A functional variant of an antibody that specifically binds to the G protein of a respiratory syncytial virus (RSV) and neutralizes RSV A2 and B strains, wherein the functional variant of an antibody is selected from the group consisting of:

a) a functional variant of 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:4, a light chain CDR2 region of SEQ ID NO:5, and a light chain CDR3 region of SEQ ID NO:6;

b) a functional variant of 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: 10, a heavy chain CDR2 region of SEQ ID NO:11, and a light chain CDR3 region of SEQ ID NO:12,

c) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO: 13, a heavy chain CDR2 region of SEQ ID NO: 14, and a heavy chain CDR3 region of SEQ ID NO:15, 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;

d) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO: 19, a heavy chain CDR2 region of SEQ ID NO:20, and a heavy chain CDR3 region of SEQ ID NO:21, 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) a functional variant of 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;

f) a functional variant of 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;

g) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:37, a heavy chain CDR2 region of SEQ ID NO:38, and a heavy chain CDR3 region of SEQ ID NO:39, a light chain CDR1 region of SEQ ID NO:40, a light chain CDR2 region of SEQ ID NO:41, and a light chain CDR3 region of SEQ ID NO:42;

h) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:43, a heavy chain CDR2 region of SEQ ID NO:44, and a heavy chain CDR3 region of SEQ ID NO:45, a light chain CDR1 region of SEQ ID NO:46, a light chain CDR2 region of SEQ ID NO:47, and a light chain CDR3 region of SEQ ID NO:48;

i) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:49, a heavy chain CDR2 region of SEQ ID NO:50 and a heavy chain CDR3 region of SEQ ID NO:51, a light chain CDR1 region of SEQ ID NO:52, a light chain CDR2 region of SEQ ID NO:53, and a light chain CDR3 region of SEQ ID NO:54;

j) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:55, a heavy chain CDR2 region of SEQ ID NO:56, and a heavy chain CDR3 region of SEQ ID NO:57 a light chain CDR1 region of SEQ ID NO:58, a light chain CDR2 region of SEQ ID NO:59, and a light chain CDR3 region of SEQ ID NO:60;

k) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:61, a heavy chain CDR2 region of SEQ ID NO:62, and a heavy chain CDR3 region of SEQ ID NO:63, a light chain CDR1 region of SEQ ID NO:64, a light chain CDR2 region of SEQ ID NO:65, and a light chain CDR3 region of SEQ ID NO:66; and

l) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO:67, a heavy chain CDR2 region of SEQ ID NO:68, and a heavy chain CDR3 region of SEQ ID NO:69 a light chain CDR1 region of SEQ ID NO:70, a light chain CDR2 region of SEQ ID NO:71, and a light chain CDR3 region of SEQ ID NO:72.

4. An immunoconjugate comprising:

the antibody of claim 1 , and

at least one therapeutic agent and/or detectable agent.

5. A nucleic acid molecule encoding a peptide comprising the antigen-binding fragment of claim 2 .

6. A vector comprising at least one nucleic acid molecule of claim 5 .

7. A host cell comprising at least one vector of claim 6 .

8. A method of producing an antibody, an antigen-binding fragment, and/or a functional variant, wherein the method comprises the steps of:

a) culturing the host cell of claim 7 under conditions conducive to the expression of the antibody, and optionally,

b) recovering the expressed antibody, antigen-binding fragment and/or functional variant.

9. A pharmaceutical composition comprising:

the antibody of claim 1 , and

at least one pharmaceutically acceptable excipient.

10. A medicament comprising:

the functional variant of claim 3 , and

at least one pharmaceutically acceptable excipient.

11. A method of prophylaxing against and/or treating a subject with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the antigen-binding fragment of claim 2 in prophylaxis or treatment, or combination thereof, of RSV infection.

12. A kit comprising at least the antigen-binding fragment of claim 2 .

13. A method of detecting RSV infection, the method comprising:

assaying a level of RSV antigen in a sample with the antibody of claim 1 ; 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.

14. An immunoconjugate comprising:

the antibody antigen-binding fragment of claim 2 , and

at least one therapeutic agent and/or detectable agent.

15. An immunoconjugate comprising:

the functional variant of claim 3 , and

at least one therapeutic agent and/or detectable agent.

16. A method of prophylaxing against and/or treating a subject diagnosed with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the antibody of claim 1 in the prophylaxis and/or treatment of the RSV infection.

17. A method of prophylaxing against and/or treating a subject diagnosed with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the functional variant of claim 3 in the prophylaxis and/or treatment of the RSV infection.

18. The antibody of claim 1 , wherein the antibody comprises 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:10, a heavy chain CDR2 region of SEQ ID NO: 11, and a light chain CDR3 region of SEQ ID NO: 12.