DNA monoclonal antibodies targeting influenza virus
Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an anti-influenza-hemagglutinin synthetic antibody. The disclosure also provides a method of preventing and/or treating influenza in a subject using said composition and method of generation.
1. A nucleic acid molecule encoding one or more synthetic antibodies, wherein the nucleic acid molecule comprises at least one selected from the group consisting of
a) a nucleotide sequence encoding an anti-influenza hemagglutinin (HA) synthetic antibody; and
b) a nucleotide sequence encoding a fragment of an anti-influenza-HA synthetic antibody;
wherein the anti-influenza HA synthetic antibody comprises an amino acid sequence selected from the group consisting of a sequence at least 90% identical to SEQ ID NOs:1-8, and a functional fragment thereof.
2. The nucleic acid molecule of claim 1 , wherein the anti-influenza HA synthetic antibody is selected from the group consisting of an antibody that binds to the globular head of influenza HA and an antibody that binds to the fusion subdomain of influenza HA.
3. The nucleic acid molecule of claim 1 , wherein nucleic acid molecule encodes an anti-influenza HA synthetic antibody comprising an amino acid sequence selected from a sequence at least 95% identical to SEQ ID NOs:1-8, and a fragment thereof.
4. The nucleic acid molecule of claim 3 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from a sequence at least 90% identical to SEQ ID NOs: 9-16 and a fragment thereof.
5. The nucleic acid molecule of claim 1 , comprising at least one nucleotide sequence selected from the group consisting of a first nucleotide sequence encoding a first anti-influenza-HA antibody; and a second nucleotide sequence encoding a second anti-influenza-HA antibody.
6. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a cleavage domain.
7. The nucleic acid molecule of claim 1 , comprising a nucleotide sequence encoding a variable heavy chain region and a variable light chain region of a anti-influenza-HA antibody.
8. The nucleic acid molecule of claim 1 , comprising a nucleotide sequence encoding a constant heavy chain region and a constant light chain region of human IgG1κ.
9. The nucleic acid molecule of claim 1 , comprising a nucleotide sequence encoding a polypeptide comprising a variable heavy chain region of anti-influenza-HA; a constant heavy chain region of human IgG1κ; a cleavage domain; a variable light chain region of anti-influenza-HA; and a constant light chain region of IgG1κ.
10. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a leader sequence.
11. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises an expression vector.
12. A composition comprising the nucleic acid molecule of claim 1 .
13. The composition of claim 12 , further comprising a pharmaceutically acceptable excipient.
14. A method of treating an influenza infection in a subject, the method comprising administering to the subject the nucleic acid molecule of claim 1 .
15. The method of claim 14 , wherein the influenza infection is selected from an influenza A infection and an influenza B infection.
16. A method of treating an influenza infection in a subject, the method comprising administering to the subject a composition of claim 12 .