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 immunogenic peptides. Also disclosed are immunogenic peptides comprising fragments of gp350 amino acid sequence, EBV antibody-small molecule conjugates and pharmaceutical compositions comprising the antibody or an immunogenic fragment thereof, one or more immunogenic peptides, or the EBV antibody-small molecule conjugate. The antibodies, immunogenic peptides, conjugates, and pharmaceutical compositions can be used to treat or prevent EBV infections and EBV-associated conditions and diseases.

1 . An antibody or an immunogenic fragment thereof that specifically binds to Epstein-Barr virus (EBV) glycoprotein (gp) 350 or glycoprotein 220. 
     
     
         2 . The antibody or the immunogenic fragment thereof of  claim 1 , wherein the antibody or the immunogenic fragment thereof specifically binds to a fragment of gp350 comprising the amino acid sequence of AA1-101, 102-201, or 402-501. 
     
     
         3 . The antibody or the immunogenic fragment thereof of  claim 1 , comprising a VH region comprising CDR1, CDR2 and CDR3 having an amino acid sequence of SEQ ID NOs: 5-19, 21-35, and 37-51. 
     
     
         4 . The antibody or the immunogenic fragment thereof of  claim 1 , comprising a VL region comprising CDR1, CDR2 and CDR3 having an amino acid sequence of SEQ ID NOs: 53-67, 69-83, and 85-99. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody is a chimeric antibody, a humanized antibody or a human antibody. 
     
     
         7 . The antibody of  claim 6 , wherein the antibody is humanized 72A1 or humanized E1D1. 
     
     
         8 . An immunogenic peptide comprising one or more fragments of gp350, wherein each fragment has an amino acid sequence identical to or sharing at least 60% similarity to AA1-101, AA102-201 or AA402-501. 
     
     
         9 . The immunogenic peptide of  claim 8 , further comprising a known immunogenic peptide such as keyhole limpet hemocyanin (KLH) peptide. 
     
     
         10 . An antibody-small molecule conjugate comprising:
 the antibody or the immunogenic fragment thereof of  claim 1 ; 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 11 , 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 L 2 P 4 , 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 antibody or the immunogenic fragment thereof of  claim 1 . 
     
     
         18 . A method of neutralizing EBV infection, preventing EBV infection, preventing a post-transplant lymphoproliferative disease (PTLD), or treating an EBV-associated cancer, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody or the immunogenic fragment thereof of  claim 1 . 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 18 , wherein the subject is a pediatric transplant recipient who is EBV naïve or an adult transplant recipient. 
     
     
         22 . The method of  claim 21 , wherein the administration is before, during, and/or after the transplant. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 18 , wherein the EBV-associated cancer is selected from the group consisting of Hodgkin lymphoma, Burkitt lymphoma, gastric cancer, and nasopharyngeal carcinoma. 
     
     
         25 - 29 . (canceled)