Epstein-barr virus antibodies and uses thereof

Abstract

Disclosed herein are antibodies or immunogenic fragments thereof that specifically bind to Epstein-Barr virus (EBV) glycoprotein 350 (gp350) or 220 or one or more epitopes of EBV gp350 and neutralize EBV infection. Also disclosed are immunogenic peptides comprising one or more gp350 epitopes, EBV antibody-small molecule conjugates and pharmaceutical compositions comprising the antibody or an immunogenic fragment thereof, one or more epitopes of EBV gp350, one or more immunogenic peptides, or the EBV antibody-small molecule conjugate. The antibodies, epitopes, immunogenic peptides, conjugates, and pharmaceutical compositions can be used to treat or prevent EBV infections and EBV-associated conditions and diseases.

1 - 4 . (canceled) 
     
     
         5 . The antibody of  claim 30 , wherein the antibody is a monoclonal antibody. 
     
     
         6 . The antibody of  claim 30 , wherein the antibody is a chimeric antibody, a humanized antibody or a human antibody. 
     
     
         7 . An immunogenic peptide comprising one or more gp350 epitopes, wherein each epitope has an amino acid sequence identical to or sharing at least 60% similarity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. 
     
     
         8 . The immunogenic peptide of  claim 7 , comprising a first domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO:1, a second domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 2, and a third domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 3. 
     
     
         9 . The immunogenic peptide of  claim 7 , comprising a first domain comprising an amino acid sequence having at least 60% similarity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, and a second domain comprising a known immunogenic peptide such as keyhole limpet hemocyanin (KLH) peptide. 
     
     
         10 . An antibody-small molecule conjugate comprising:
 a V H  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-19, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 20-35, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-51;   a V L  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52-67, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 68-83, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 84-99; and   a small molecule having an anti-proliferative activity against EBV-transformed cells,   wherein the small molecule is conjugated to the antibody.   
     
     
         11 . The conjugate of  claim 10 , wherein the antibody is a monoclonal antibody. 
     
     
         12 . The conjugate of  claim 10 , wherein the antibody is a chimeric antibody, a humanized antibody or a human antibody. 
     
     
         13 . The conjugate of  claim 10 , wherein the small molecule is a growth inhibitor of EBV infected B cells. 
     
     
         14 . The conjugate of  claim 10 , wherein the small molecule is L2P4, 2-butynediamide, or a derivative thereof. 
     
     
         15 . The conjugate of  claim 10 , wherein the small molecule is conjugated to the antibody via a linker or an adaptor. 
     
     
         16 . The conjugate of  claim 10 , wherein the small molecule is conjugated to the constant region of the heavy chain or the light chain of the antibody. 
     
     
         17 . A pharmaceutical composition comprising the immunogenic peptide of  claim 7 . 
     
     
         18 . A method of neutralizing EBV infection comprising administering to a subject infected with EBV a therapeutically effective amount an antibody or an immunogenic fragment thereof comprising:
 a V H  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-19, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 20-35, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-51; and   a V L  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52-67, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 68-83, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 84-99.   
     
     
         19 . A method of preventing EBV infection comprising administering to a subject at an elevated risk of EBV infection a therapeutically effective amount of the antibody or the immunogenic fragment thereof of claim  1 . 
     
     
         20 . A method of preventing a post-transplant lymphoproliferative disease (PTLD) comprising administering to a subject who is a transplant recipient a therapeutically effective amount of the antibody or the immunogenic fragment thereof of claim  1 . 
     
     
         21 - 22 . (canceled) 
     
     
         23 . A method of treating an EBV-associated cancer comprising administering to a subject suffering from an EBV-associated cancer a therapeutically effective amount of the antibody or the immunogenic fragment thereof of claim  1 . 
     
     
         24 . (canceled) 
     
     
         25 . A method of immunizing or vaccinating a subject against EBV infection comprising administering to the subject a therapeutically effective amount of the immunogenic peptide of  claim 7 , or a pharmaceutical composition thereof. 
     
     
         26 . A method of inducing the production of neutralizing antibodies against a EBV in a subject, comprising administering an effective amount of a gp350 epitope represented by SEQ ID NO: 3 or an immunogenic peptide comprising SEQ ID NO: 3. 
     
     
         27 - 29 . (canceled) 
     
     
         30 . An antibody or an immunogenic fragment thereof comprising:
 a V H  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-19, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 20-35, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-51; and   a V L  region comprising CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52-67, CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 68-83, and CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 84-99.