Multi-specific antibodies for cross-neutralization of multiple filovirus glycoproteins
Methods for treating and for preventing filovirus infections are disclosed, as well as compositions therefor.
1. A method of treating a filovirus infection in a subject comprising administering an amount of a composition to the subject effective to treat a filovirus infection in a subject, wherein the composition comprises: (1) a first single chain variable fragment (scFv) comprising at least one complementarity-determining region (CDR) directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, which first scFv is covalently joined to (2) a first polypeptide of an immunoglobulin G (IgG) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, wherein the first species of filovirus and second species of filovirus are different species, wherein the first scFv comprises (i) SEQ ID NOS: 9 and 11, or (ii) SEQ ID NOS: 13 and 15, and wherein the IgG comprises (i) SEQ ID NOS: 13 and 15, or SEQ ID NOS: 9 and 11, respectively.
2. The method of claim 1 , wherein the first scFv is covalently joined at its N terminal to a C terminal of a first polypeptide of the IgG.
3. The method of claim 2 , wherein the first polypeptide of the IgG is a heavy chain or a light chain.
4. The method of claim 1 , wherein the first scFv is covalently joined at its C terminus to an N terminus of a first polypeptide of the IgG.
5. The method of claim 4 , wherein the first polypeptide of the IgG is a heavy chain or a light chain.
6. The method of claim 1 , wherein the scFv is covalently joined to the first polypeptide via a polypeptide linker.
7. The method of claim 6 , wherein the polypeptide linker comprises the sequence GGSAGSAGSAGSGGS (SEQ ID NO:17).
8. The method of claim 1 , wherein a V H sequence of the first scFv has a sequence identical to V H sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus.
9. The method of claim 1 , wherein a V L sequence of the first scFv has a sequence identical to V L sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus.
10. The method of claim 8 , wherein the V H sequence of the scFv is joined to the V L sequence of the first scFv by a polypeptide linker.
11. The method of claim 10 , wherein the polypeptide linker is majority glycine residues.
12. The method of claim 10 , wherein the polypeptide linker is GGGGSGGGGSGGGGS (SEQ ID NO:18).
13. The method of claim 1 , wherein the composition comprises a second scFv, wherein the second scFv is covalently joined to a second polypeptide of the IgG.