Antibody molecules to dengue virus and uses thereof
Antibody molecules that specifically bind to dengue virus are disclosed. In certain embodiments, the antibody molecule bind to dengue virus serotypes DV-1, DV-2, DV-3, and DV-4. The antibody molecules can be used to treat, prevent, and/or diagnose dengue virus.
1. A nucleic acid molecule comprising a first nucleotide sequence encoding a heavy variable region of an antibody molecule capable of binding dengue virus, wherein the antibody molecule comprises:
(a) a heavy chain immunoglobulin variable region segment comprising:
a CDR1 comprising the sequence DVYMS (SEQ ID NO: 3),
a CDR2 comprising the sequence RIDPENGDTKYDPKLQG (SEQ ID NO: 4), and
a CDR3 comprising the sequence GWEGFAY (SEQ ID NO: 5); and
(b) a light chain immunoglobulin variable region segment comprising:
a CDR1 comprising the sequence RASENVDKYGNSFMH (SEQ ID NO: 6),
a CDR2 comprising the sequence RASELQW (SEQ ID NO: 7), and
a CDR3 comprising the sequence QRSNEVPWT (SEQ ID NO: 8).
2. An expression vector comprising the nucleic acid molecule of claim 1 .
3. An isolated host cell comprising the nucleic acid molecule of claim 1 .
4. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH FW1 having the sequence QVQLVQSGAEVKKPGASVKVSCKAGFNIK (SEQ ID NO: 11).
5. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH FW2 having the sequence WVRQAPGQGLEWMG (SEQ ID NO: 84) or WVRQAPEQGLEWMG (SEQ ID NO: 85).
6. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH FW1 comprising a deletion of position 26 relative to SEQ ID NO: 33.
7. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH amino acid sequence at least 85% identical to SEQ ID NO: 1.
8. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises the VH amino acid sequence of SEQ ID NO: 1.
9. The nucleic acid molecule of claim 1 , wherein the first nucleotide sequence encodes a VH amino acid sequence at least 85% identical to SEQ ID NO: 1.
10. The nucleic acid molecule of claim 1 , wherein the first nucleotide sequence encodes the VH amino acid sequence of SEQ ID NO: 1.
11. The nucleic acid molecule of claim 1 , which comprises a VH nucleotide sequence at least 85% identical to SEQ ID NO: 37.
12. The nucleic acid molecule of claim 1 , which comprises the VH nucleotide sequence of SEQ ID NO: 37.
13. The nucleic acid molecule of claim 1 , further comprising a second nucleotide sequence encoding a light chain variable region of the antibody molecule.
14. The nucleic acid molecule of claim 13 , wherein the antibody molecule comprises a VL amino acid sequence at least 85% identical to SEQ ID NO: 2.
15. The nucleic acid molecule of claim 13 , wherein the antibody molecule comprises the VL amino acid sequence of SEQ ID NO: 2.
16. The nucleic acid molecule of claim 13 , wherein the antibody molecule comprises the VH amino acid sequence of SEQ ID NO: 1 and the VL amino acid sequence of SEQ ID NO: 2.
17. The nucleic acid molecule of claim 13 , wherein the second nucleotide sequence encodes a VL amino acid sequence at least 85% identical to SEQ ID NO: 2.
18. The nucleic acid molecule of claim 13 , wherein the second nucleotide sequence encodes the VL amino acid sequence of SEQ ID NO: 2.
19. The nucleic acid molecule of claim 13 , which the first nucleotide sequence encodes the VH amino acid sequence of SEQ ID NO: 1 and the second nucleotide sequence encodes the VL amino acid sequence of SEQ ID NO: 2.
20. The nucleic acid molecule of claim 13 , which comprises a VL nucleotide sequence at least 85% identical to SEQ ID NO: 38.
21. The nucleic acid molecule of claim 13 , which comprises the VL nucleotide sequence of SEQ ID NO: 38.
22. The nucleic acid molecule of claim 13 , which comprises the VH nucleotide sequence of SEQ ID NO: 37 and the VL nucleotide sequence of SEQ ID NO: 38.
23. A nucleic acid molecule comprising a first nucleotide sequence encoding the VH amino acid sequence of SEQ ID NO: 1, a second nucleotide sequence encoding the VL amino acid sequence of SEQ ID NO: 2, or both.
24. A nucleic acid molecule comprising the VH nucleotide sequence of SEQ ID NO: 37, the VL nucleotide sequence of SEQ ID NO: 38, or both.
25. An expression vector comprising the nucleic acid molecule of claim 13 .
26. An expression vector comprising the nucleic acid molecule of claim 23 .
27. An expression vector comprising the nucleic acid molecule of claim 24 .
28. An isolated host cell comprising the nucleic acid molecule of claim 13 .
29. An isolated host cell comprising the nucleic acid molecule of claim 23 .
30. An isolated host cell comprising the nucleic acid molecule of claim 24 .