Parvovirus antibodies for veterinary use
Provided are various embodiments relating to parvovirus antibodies, including caninized, felinized, and chimeric antibodies, that bind to canine and/or feline parvovirus, for example, having improved expression characteristics. In various embodiments, the parvovirus antibodies have ADCC, ADCP, and/or CDC effector functions. In various embodiments, such monoclonal parvovirus antibodies can be used in methods to prevent and/or treat parvoviral infection in subjects, such as dogs and cats. For example, the parvovirus antibodies provided may be used to provide passive immunity against infection with a canine or feline parvovirus.
1. An antibody that binds to canine parvovirus and/or feline parvovirus, wherein the antibody comprises:
(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4,
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5,
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6, and
(b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13,
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14,
(iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15, and
wherein the heavy chain sequence is at least 95% identical to SEQ ID NO: 24 and the light chain sequence is at least 95% identical to SEQ ID NO: 25.
2. The antibody of claim 1 , wherein the heavy chain sequence is at least 98% identical to SEQ ID NO: 24 and the light chain sequence is at least 98% identical to SEQ ID NO: 25.
3. The antibody of claim 1 , wherein the heavy chain sequence is at least 99% identical to SEQ ID NO: 24 and the light chain sequence is at least 99% identical to SEQ ID NO: 25.
4. The antibody of claim 1 , wherein said antibody is isolated.
5. The antibody of claim 1 , wherein said antibody is a chimeric antibody.
6. The antibody of claim 1 , wherein the antibody binds to an epitope comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and/or SEQ ID NO: 3.
7. The antibody of claim 1 , wherein the antibody binds to canine parvovirus or feline parvovirus as determined by immunoblot analysis and/or biolayer interferometry.
8. The antibody of claim 1 , wherein the antibody at a concentration of 200 μg/mL has an hemagglutination inhibition value of at least 8000, of at least 16000, or of at least 32000.
9. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
10. An isolated nucleic acid encoding the antibody of claim 1 .
11. A host cell comprising the nucleic acid of claim 10 .
12. A method of producing an antibody comprising culturing the host cell of claim 11 and isolating the antibody.
13. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , wherein the pharmaceutically acceptable carrier is phosphate buffered saline.
15. A method of providing passive immunity in a canine or a feline subject against infection with a canine or feline parvovirus comprising administering to the subject a therapeutically effective amount of the antibody of claim 1 that binds to the canine or feline parvovirus.
16. The method of claim 15 , wherein the antibody is administered before or after exposure to the canine or feline parvovirus or after infection with the canine or feline parvovirus.
17. The method of claim 16 , wherein the antibody is administered after the subject has exhibited at least one symptoms selected from the group consisting of fever, vomiting, diarrhea, lymphopenia, and septicemia.
18. An antibody that binds to canine parvovirus and/or feline parvovirus, wherein the antibody comprises:
(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4,
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5,
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6, and
(b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13,
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14,
(iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15, and
wherein the heavy chain sequence comprises SEQ ID NO: 24 with optionally 1, 2, 3, 4, or 5 amino acid substitutions and the light chain sequence comprises SEQ ID NO: 25 with optionally 1, 2, 3, 4, or 5 amino acid substitutions.
19. The antibody of claim 18 , wherein said amino acid substitutions are conservative substitutions.
20. A method of treating a canine or feline parvoviral infection in a canine or a feline subject comprising administering to the subject a therapeutically effective amount of the antibody of claim 1 that binds to the canine or feline parvovirus.
21. A method for detecting a parvoviral infection in a sample from a canine or a feline subject comprising contacting the sample with the antibody of claim 1 under conditions permissive for the binding of the antibody to a parvovirus, and detecting whether a complex is formed between the antibody and the parvovirus in the sample.
22. A variant IgG Fc polypeptide comprising:
a) an aspartic acid or a glutamic acid at a position corresponding to position 10 of SEQ ID NO: 91;
b) an aspartic acid or a glutamic acid at position 10 of SEQ ID NO: 91;
c) an aspartic acid or a glutamic acid at a position corresponding to position 103 of SEQ ID NO: 91;
d) an aspartic acid or a glutamic acid at position 103 of SEQ ID NO: 91;
e) an aspartic acid or a glutamic acid at a position corresponding to position 10 and/or position 103 of SEQ ID NO: 91; or
f) an aspartic acid or a glutamic acid at position 10 and/or position 103 of SEQ ID NO: 91.
23. The antibody of claim 1 , wherein the heavy chain comprises a variable heavy chain framework region (HC-FR1) comprising the amino acid sequence of SEQ ID NO: 8.
24. The antibody of claim 2 , wherein the heavy chain comprises a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 8.
25. The antibody of claim 19 , wherein the heavy chain comprises a HC-FR1 comprising the amino acid sequence of SEQ ID NO: 8.
26. The antibody of claim 18 , wherein the antibody comprises:
(a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4,
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5,
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6, and
(b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13,
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14,
(iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 15, and
wherein the heavy chain sequence comprises SEQ ID NO: 24 and the light chain sequence comprises SEQ ID NO: 25.
27. The antibody of claim 1 , wherein the antibody binds to canine parvovirus.
28. The antibody of claim 19 , wherein the antibody binds to canine parvovirus.