Plant-produced mABs against chikungunya virus with enhanced effector function and efficacy
AssigneeArizona Board of Regents on behalf of Arizona State University
InventorsQiang Chen, Jonathan Hurtado, Haiyan Sun, Huafang Lai
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Abstract
Disclosed are monoclonal antibodies against Chikungunya virus having enhanced effector function and efficacy, methods of producing them, and methods of treatment of Chikungunya viral infection using the antibodies.
Claims11
A glycosylated IgG monoclonal antibody having specificity to Chikungunya virus (CHIKV) E1 or E2 protein, comprising a heavy chain and a light chain pair selected from:
- (a) a heavy chain comprising the amino acid sequence of SEQ. ID NO:
- 3;
- and a light chain comprising the amino acid sequence of SEQ. ID NO:
- 5;
- (b) a heavy chain comprising the amino acid sequence of SEQ. ID NO:
- 7;
- and a light chain comprising the amino acid sequence of SEQ. ID NO:
- 9;
- (c) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 11;
- and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 13;
- or
- (d) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 15;
- and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 17;
- wherein the Fc domain of the heavy chain is characterized by an N-linked glycan profile comprising an N-linked GlcNAc2Man3GlcNAc2 (GnGn) core glycan (Man=Mannose, GlcNAc=N-acetylglucosamine) with more than about 95% uniformity.
A composition for the prevention or treatment of Chikungunya, the composition comprising a prophylactically or therapeutically effective amount of a glycosylated monoclonal antibody having specificity to CHIKV E1 or E2 protein, wherein the antibody comprises a heavy chain and a light chain pair selected from:
- (a) a heavy chain comprising the amino acid sequence of SEQ. ID NO:
- 3;
- and a light chain comprising the amino acid sequence of SEQ. ID NO:
- 5;
- (b) a heavy chain comprising the amino acid sequence of SEQ. ID NO:
- 7;
- and a light chain comprising the amino acid sequence of SEQ. ID NO:
- 9;
- (c) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 11;
- and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 13;
- or
- (d) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 15;
- and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 17;
- wherein the Fc domain of the heavy chain is characterized by an N-linked glycan profile comprising an N-linked GlcNAc2Man3GlcNAc2 (GnGn) core glycan (Man=Mannose, GlcNAc=N-acetylglucosamine) with more than about 95% uniformity.
A method of producing a glycosylated monoclonal antibody having specificity to CHIKV E1 or E2 protein, the method comprising introducing into a plant expression system, one or more vectors for the expression of an anti-CHIKV E1 or E2 antibody, wherein the vector comprises a nucleic acid sequence encoding a heavy chain and a light chain pair selected from:
- (a) a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 2 and a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 4;
- (b) a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 6 and a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 8;
- (c) a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 10 and a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 12;
- or
- (d) a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 14 and a nucleic acid sequence set forth in the sequence of SEQ ID NO:
- 16;
- wherein the Fc domain of the heavy chain is characterized by an N-linked glycan profile comprising an N-linked GlcNAc2Man3GlcNAc2 (GnGn) core glycan (Man=Mannose, GlcNAc=N-acetylglucosamine) with more than about 95% uniformity.
Dependencies are inferred from the claim text.