Antibody-mediated neutralization of marburg virus

Abstract

The present disclosure is directed to antibodies binding to Marburg virus (MARV) glycoprotein (GP) and methods of use therefore.

1 . A method of detecting a filovirus infection in a subject comprising:
 (a) contacting sample from said subject with an antibody or antibody fragment having heavy chain CDR sequences of SEQ ID NOS: 83, 84 and 85, and light chain CDR sequences of SEQ ID NO: 136, SNT and SEQ ID NO: 137; and   (b) detecting Marburg virus glycoprotein (GP) in said sample by binding of said antibody or antibody fragment to GP in said sample.   
     
     
         2 . The method of  claim 1 , wherein said sample is a body fluid. 
     
     
         3 . The method of  claim 1 , wherein said sample is blood, sputum, tears, saliva, mucous or serum, urine or feces. 
     
     
         4 . The method of  claim 1 , wherein detection comprises ELISA, RIA or Western blot. 
     
     
         5 . The method of  claim 1 , further comprising performing steps (a) and (b) a second time and determining a change in the GP levels as compared to the first assay. 
     
     
         6 . The method of  claim 1 , wherein the antibody or antibody fragment is characterized by heavy and light chain variable sequences as set forth in SEQ ID NOS: 46 and 47, respectively. 
     
     
         7 . The method of  claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 11 and 10, respectively. 
     
     
         8 . The method of  claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 47 and 46, respectively. 
     
     
         9 . The method 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. 
     
     
         10 . The method of  claim 1 , wherein said antibody does not bind to Ebola virus. 
     
     
         11 . A method of treating a subject infected with a filovirus, or reducing the likelihood of infection of a subject at risk of contracting a filovirus, comprising delivery to said subject an antibody or antibody fragment having heavy chain CDR sequences of SEQ ID NOS: 83, 84 and 85, and light chain CDR sequences of SEQ ID NO: 136, SNT and SEQ ID NO: 137. 
     
     
         12 . The method of  claim 11 , the antibody or antibody fragment is encoded by heavy and light chain variable sequences of SEQ ID NOS: 10 and 11, respectively. 
     
     
         13 . The method of  claim 11 , the antibody or antibody fragment is comprises heavy and light chain variable sequences of SEQ ID NOS: 46 and 47, respectively. 
     
     
         14 . The method of  claim 11 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 11 and 10, respectively. 
     
     
         15 . The method of  claim 11 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 47 and 46, respectively. 
     
     
         16 . 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. 
     
     
         17 . The method of  claim 11 , wherein said antibody is an IgG. 
     
     
         18 . The method of  claim 11 , wherein said antibody is a chimeric antibody. 
     
     
         19 . The method of  claim 11 , wherein said antibody also binds to Ebola virus. 
     
     
         20 . The method of  claim 11 , wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment. 
     
     
         21 . A monoclonal antibody or fragment thereof, wherein the antibody is characterized by heavy chain CDR sequences of SEQ ID NOS: 83, 84 and 85, and light chain CDR sequences of SEQ ID NO: 136, SNT and SEQ ID NO: 137. 
     
     
         22 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences of SEQ ID NOS: 11 and 10, respectively. 
     
     
         23 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 11 and 10, respectively. 
     
     
         24 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment comprises light chain and heavy variable sequences of SEQ ID NOS: 47 and 46, respectively. 
     
     
         25 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 47 and 46, respectively. 
     
     
         26 . The monoclonal antibody or fragment thereof of  claim 21 , wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2  fragment, or Fv fragment. 
     
     
         27 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment is a chimeric antibody, or is bispecific antibody that targets a Marburg virus or Ebola virus antigen other than glycoprotein. 
     
     
         28 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a structural feature of a Marburg virus or Ebola virus particle, and (b) targets receptor binding domain of Marburg or Ebola virus. 
     
     
         29 . The monoclonal antibody or fragment thereof of  claim 28 , wherein said structural feature is a Marburg or Ebola virus glycoprotein domain other than the receptor binding domain. 
     
     
         30 . The monoclonal antibody or fragment thereof of  claim 28 , wherein said structural feature is a Marburg or Ebola virus virion structure other than the glycoprotein 
     
     
         31 . The monoclonal antibody or fragment thereof of  claim 30 , wherein said virion structure is a lipid, carbohydrate or protein. 
     
     
         32 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a structural feature of a Marburg virus or Ebola virus particle and (b) targets a host cell surface structure cells that is trafficked to endosomes. 
     
     
         33 . The monoclonal antibody or fragment thereof of  claim 32 , wherein the host cell surface structure is a virus receptor (the cholesterol transporter Niemann-Pick C1) or glycan. 
     
     
         34 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody is an IgG. 
     
     
         35 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody also binds to Ebola virus. 
     
     
         36 . The monoclonal antibody or fragment thereof of  claim 21 , wherein said antibody or antibody fragment further comprises a cell penetrating peptide or is an intrabody. 
     
     
         37 . An engineered cell producing an antibody or antibody fragment characterized by clone-paired heavy chain CDR sequences of SEQ ID NOS: 83, 84 and 85, and light chain CDR sequences of SEQ ID NO: 136, SNT and SEQ ID NO: 137. 
     
     
         38 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences of SEQ ID NOS: 11 and 10, respectively. 
     
     
         39 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 11 and 10, respectively. 
     
     
         40 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment comprises light chain and heavy variable sequences of SEQ ID NOS: 47 and 46, respectively. 
     
     
         41 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 47 and 46, respectively. 
     
     
         42 . The engineered cell of  claim 37 , wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2  fragment, or Fv fragment. 
     
     
         43 . The engineered cell of  claim 37 , wherein said antibody is a chimeric antibody. 
     
     
         44 . The engineered cell of  claim 37 , wherein said antibody is an IgG. 
     
     
         45 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment also binds to Ebola virus. 
     
     
         46 . The engineered cell of  claim 37 , wherein said antibody or antibody fragment further comprises a cell penetrating peptide or is an intrabody. 
     
     
         47 . The method of  claim 11 , wherein the filovirus is Marburg virus or Ebola virus chain CDR sequences. 
     
     
         48 . The method of  claim 47 , wherein said antibody or antibody fragment is a chimeric antibody, or is bispecific antibody that targets a Marburg virus or Ebola virus antigen other than glycoprotein. 
     
     
         49 . The method of  claim 47 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a structural feature of a Marburg virus or Ebola virus particle, and (b) targets receptor binding domain of Marburg or Ebola virus. 
     
     
         50 . The method of  claim 49 , wherein said structural feature is a Marburg or Ebola virus glycoprotein domain other than the receptor binding domain. 
     
     
         51 . The method of  claim 49 , wherein said structural feature is a Marburg or Ebola virus virion structure other than the glycoprotein 
     
     
         52 . The method of  claim 51 , wherein said virion structure is a lipid, carbohydrate or protein. 
     
     
         53 . The method of  claim 47 , wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a structural feature of a Marburg virus or Ebola virus particle and (b) targets a host cell surface structure cells that is trafficked to endosomes.