Antibody-mediated neutralization of chikungunya virus

1. A method of detecting a Chikungunya virus infection in a subject comprising:

(a) contacting a sample from said subject with an antibody or antibody fragment comprising paired heavy and light chain CDR1-3 sequences set out below:

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 135-137 (light chain);

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 138-140 (light chain);

SEQ ID NOS: 87-89 (heavy chain) and SEQ ID NOS: 144-146 (light chain);

SEQ ID NOS: 102-104 (heavy chain) and SEQ ID NOS: 159-161 (light chain);

SEQ ID NOS: 105-107 (heavy chain) and SEQ ID NOS: 162-164 (light chain);

SEQ ID NOS: 108-110 (heavy chain) and SEQ ID NOS: 165-167 (light chain);

SEQ ID NOS: 114-116 (heavy chain) and SEQ ID NOS: 171-173 (light chain);

SEQ ID NOS: 117-119 (heavy chain) and SEQ ID NOS: 174-176 (light chain); or

SEQ ID NOS: 120-122 (heavy chain) and SEQ ID NOS: 177-179 (light chain); and

(b) detecting Chikungunya virus in said sample by binding of said antibody or antibody fragment to a Chikungunya virus antigen in said sample.

2. A method of treating a subject infected with Chikungunya virus or reducing the likelihood of infection of a subject at risk of contracting Chikungunya virus, comprising treating said subject with an antibody or antibody fragment comprising paired heavy and light chain CDR1-3 sequences set out below:

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 135-137 (light chain);

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 138-140 (light chain);

SEQ ID NOS: 87-89 (heavy chain) and SEQ ID NOS: 144-146 (light chain);

SEQ ID NOS: 102-104 (heavy chain) and SEQ ID NOS: 159-161 (light chain);

SEQ ID NOS: 105-107 (heavy chain) and SEQ ID NOS: 162-164 (light chain);

SEQ ID NOS: 108-110 (heavy chain) and SEQ ID NOS: 165-167 (light chain);

SEQ ID NOS: 114-116 (heavy chain) and SEQ ID NOS: 171-173 (light chain);

SEQ ID NOS: 117-119 (heavy chain) and SEQ ID NOS: 174-176 (light chain); or

SEQ ID NOS: 120-122 (heavy chain) and SEQ ID NOS: 177-179 (light chain).

3. The method of claim 2 , wherein the antibody or antibody fragment is encoded by paired light and heavy chain variable sequences as set forth below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

4. The method of claim 2 , wherein the antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identify to paired sequences at set out below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

5. The method of claim 2 , wherein said antibody or antibody fragment comprises paired light and heavy chain variable sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

6. The method of claim 2 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to paired sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

7. The method of claim 2 , wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.

8. The method of claim 2 , wherein said antibody is an IgG.

9. The method of claim 2 , wherein said antibody is a chimeric antibody.

10. The method of claim 2 , wherein said antibody or antibody fragment is administered prior to infection.

11. The method of claim 2 , wherein said antibody or antibody fragment is administered after infection.

12. The method of claim 2 , wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment.

13. A hybridoma or engineered cell encoding an antibody or antibody fragment comprising paired heavy and light chain CDR1-3 sequences as set out below:

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 135-137 (light chain);

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 138-140 (light chain);

SEQ ID NOS: 87-89 (heavy chain) and SEQ ID NOS: 144-146 (light chain);

SEQ ID NOS: 102-104 (heavy chain) and SEQ ID NOS: 159-161 (light chain);

SEQ ID NOS: 105-107 (heavy chain) and SEQ ID NOS: 162-164 (light chain);

SEQ ID NOS: 108-110 (heavy chain) and SEQ ID NOS: 165-167 (light chain);

SEQ ID NOS: 114-116 (heavy chain) and SEQ ID NOS: 171-173 (light chain);

SEQ ID NOS: 117-119 (heavy chain) and SEQ ID NOS: 174-176 (light chain); or

SEQ ID NOS: 120-122 (heavy chain) and SEQ ID NOS: 177-179 (light chain).

14. The hybridoma or engineered cell of claim 13 , wherein said antibody or antibody fragment is encoded by paired light and heavy chain variable sequences as set out below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

15. The hybridoma or engineered cell of claim 13 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identity to paired variable sequences as set out below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

16. The hybridoma or engineered cell of claim 13 , wherein said antibody or antibody fragment comprises paired light and heavy chain variable sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

17. The hybridoma or engineered cell of claim 13 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to paired sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

18. A method of determining the antigenic integrity of an antigen comprising:

(a) contacting a sample comprising said antigen with a first antibody or antibody fragment comprising paired heavy and light chain CDR1-3 sequences as set out below:

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 135-137 (light chain);

SEQ ID NOS: 81-83 (heavy chain) and SEQ ID NOS: 138-140 (light chain);

SEQ ID NOS: 87-89 (heavy chain) and SEQ ID NOS: 144-146 (light chain);

SEQ ID NOS: 102-104 (heavy chain) and SEQ ID NOS: 159-161 (light chain);

SEQ ID NOS: 105-107 (heavy chain) and SEQ ID NOS: 162-164 (light chain);

SEQ ID NOS: 108-110 (heavy chain) and SEQ ID NOS: 165-167 (light chain);

SEQ ID NOS: 114-116 (heavy chain) and SEQ ID NOS: 171-173 (light chain);

SEQ ID NOS: 117-119 (heavy chain) and SEQ ID NOS: 174-176 (light chain); or

SEQ ID NOS: 120-122 (heavy chain) and SEQ ID NOS: 177-179 (light chain); and

(b) determining antigenic integrity of said antigen by detectable binding of said antibody or antibody fragment to said antigen.

19. The method of claim 1 , wherein said sample is a body fluid.

20. The method of claim 1 , wherein said sample is blood, sputum, tears, saliva, mucous or serum, urine or feces.

21. The method of claim 1 , wherein detection comprises ELISA, RIA or Western blot.

22. The method of claim 1 , further comprising performing steps (a) and (b) a second time and determining a change in the Chikungunya virus antigen levels as compared to the first assay.

23. The method of claim 1 , wherein said antibody or antibody fragment is encoded by paired light and heavy chain variable sequences as set out below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

24. The method of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having at least 95% identity to paired sequences as set out below:

SEQ ID NOS: 1 or 7 and 6; SEQ ID NOS: 11 and 10; SEQ ID NOS: 21 and 20; SEQ ID NOS: 23 and 22; SEQ ID NOS: 25 and 24; SEQ ID NOS: 29 and 28; SEQ ID NOS: 31 and 30; or SEQ ID NOS: 33 and 32.

25. The method of claim 1 , wherein said antibody or antibody fragment comprises paired light and heavy chain variable sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

26. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to paired sequences as set out below:

SEQ ID NOS: 44 or 43 and 42; SEQ ID NOS: 48 and 47; SEQ ID NOS: 58 and 57; SEQ ID NOS: 60 and 59; SEQ ID NOS: 62 and 61; SEQ ID NOS: SEQ ID NOS: 66 and 65; SEQ ID NOS: 68 and 67; or SEQ ID NOS: 70 and 69.

27. The method of claim 1 , wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.