Antibody-mediated neutralization of Marburg virus
The present disclosure is directed to antibodies binding to Marburg virus (MARV) glycoprotein (GP) and methods of use therefore.
1. An engineered cell producing an antibody or antibody fragment characterized by heavy chain CDR sequences of SEQ ID NOS: 104, 105 and 106 and light chain CDR sequences of SEQ ID NO: 150, DNN and SEQ ID NO: 151.
2. The engineered cell of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences comprising SEQ ID NO: 25 and SEQ ID NO: 24, respectively.
3. The engineered cell of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 90% identity to SEQ ID NO: 25 and SEQ ID NO: 24, respectively.
4. The engineered cell of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences of SEQ ID NO: 61 and SEQ ID NO: 60, respectively.
5. The engineered cell of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NO: 61 and SEQ ID NO: 60, respectively.
6. The engineered cell of claim 1 , wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.
7. The engineered cell of claim 1 , wherein said antibody is a chimeric antibody.
8. The engineered cell of claim 1 , wherein said antibody is an IgG.
9. The engineered cell of claim 1 , wherein said antibody or antibody fragment also binds to Ebola virus.
10. The engineered cell of claim 1 , wherein said antibody or antibody fragment further comprises a cell penetrating peptide or is an intrabody.
11. A method of inhibiting a Marburg virus or Ebola virus in a subject comprising delivery to said subject an antibody or antibody fragment having heavy chain CDR sequences of SEQ ID NOS: 104, 105 and 106 and light chain CDR sequences of SEQ ID NO: 150, DNN and SEQ ID NO: 151.
12. The method of claim 11 , wherein said antibody or antibody fragment is a chimeric antibody or is bispecific antibody.
13. The method of claim 12 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets glycoprotein of a Marburg virus or Ebola virus, and (b) targets a structural feature of a Marburg or Ebola virus particle.
14. The method of claim 13 , wherein said structural feature is a Marburg or Ebola virus glycoprotein domain other than the receptor binding domain.
15. The method of claim 13 , wherein said structural feature is a Marburg or Ebola virus virion structure other than the glycoprotein.
16. The method of claim 15 , wherein said virion structure is a lipid, carbohydrate or protein.
17. The method of claim 11 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a glycoprotein of a Marburg virus or Ebola virus particle and (b) targets a host cell surface structure cells that is trafficked to endosomes.
18. The method of claim 11 , wherein said subject is infected with a Marburg virus.
19. The method of claim 11 , wherein said subject is infected with an Ebola virus.
20. The method of claim 11 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences comprising SEQ ID NO: 25 and SEQ ID NO: 24, respectively.
21. The engineered cell of claim 11 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences of SEQ ID NO: 61 and SEQ ID NO: 60, respectively.
22. The method of claim 11 , wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.
23. The method of claim 11 , wherein said antibody is a chimeric antibody.
24. The method of claim 11 , wherein said antibody is an IgG.