Antibodies that bind zika virus envelope protein and uses thereof

Abstract

Isolated monoclonal antibodies which bind to Zika virus envelope protein and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic and diagnostic methods for using the antibodies.

1 . A method for treating or preventing Zika virus infection in a subject, comprising administering to the subject in need thereof, an effective amount of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen binding portion thereof has neutralizing activity against Zika virus. 
     
     
         3 . The method of  claim 1 , wherein the antibody or antigen binding portion thereof is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgD, and an IgE antibody. 
     
     
         4 . The method of  claim 1 , wherein the antibody or antigen binding portion thereof comprises a heavy chain variable region, wherein the heavy chain variable region comprises a lysine at position 82B, numbering according to Chothia. 
     
     
         5 . The method of  claim 4 , wherein the antibody or antigen binding portion thereof is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgD, and an IgE antibody. 
     
     
         6 . The method of  claim 1 , wherein the antibody or antigen binding portion thereof comprises heavy and light chain variable regions comprising the amino acid sequences of SEQ ID NOs: 6 and 15, respectively. 
     
     
         7 . The method  claim 6 , wherein the antibody or antigen binding portion thereof is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgD, and an IgE antibody. 
     
     
         8 . The method of  claim 1 , wherein the antibody or antigen binding portion thereof is formulated as a pharmaceutical composition. 
     
     
         9 . A method for treating, preventing, reducing, or reducing the risk of vertical Zika virus infection to a fetus in a pregnant subject, comprising administering to the subject an effective amount of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         10 . The method of  claim 9 , wherein the pregnant subject is infected with a Zika virus or the pregnant subject is at risk of Zika virus infection. 
     
     
         11 . A method for treating, preventing, reducing, or reducing the risk of fetal Zika virus infection, comprising administering to a pregnant subject in need thereof, an effective amount of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         12 . The method of  claim 11 , wherein the pregnant subject is infected with Zika virus or the pregnant subject is at risk of being infected with Zika virus. 
     
     
         13 . A method for treating, preventing, reducing, or reducing the risk of fetal mortality in a pregnant subject, comprising administering to the subject an effective amount of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         14 . The method of  claim 13 , wherein the pregnant subject is infected with Zika virus or the pregnant subject is at risk of being infected with Zika virus. 
     
     
         15 . A method for treating, preventing, reducing, or reducing the risk of placental Zika virus infection, comprising administering to a pregnant subject in need thereof, an effective amount of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         16 . The method of  claim 15 , wherein the pregnant subject is infected with Zika virus or the pregnant subject is at risk of being infected with Zika virus. 
     
     
         17 . A nucleic acid comprising a nucleotide sequence encoding the light chain, heavy chain, or both light and heavy chains of an isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
 (i) heavy chain CDR1 comprises GFSFSTY (SEQ ID NO: 21);   (ii) heavy chain CDR2 comprises SGEGDS (SEQ ID NO: 27);   (iii) heavy chain CDR3 comprises GYSNFYYYYTMDA (SEQ ID NO: 32);   (iv) light chain CDR1 comprises RATQSISTFLA (SEQ ID NO: 38);   (v) light chain CDR2 comprises DASTRAS (SEQ ID NO: 44); and   (vi) light chain CDR3 comprises QQRYNWPPYS (SEQ ID NO: 50).   
     
     
         18 . An expression vector comprising the nucleic acid of  claim 17 . 
     
     
         19 . A cell transformed with an expression vector of  claim 18 .