Epstein Barr virus antibodies, vaccines, and uses of the same
Anti-Epstein Barr Virus (EBV) antibodies and vaccines are described herein. The antibodies and vaccines can be used to treat and/or reduce the risk of EBV infection and to treat and/or reduce the risk of complications associated with EBV infection, such as infectious mononucleosis, lymphoproliferative disorders, carcinomas, and smooth muscle tumors.
1. An anti-EBV antibody comprising:
(i) variable light chain complementary determining regions (CDRs) having the sequences as set forth in SEQ ID NO: 11 for CDRL1, SEQ ID NO: 12 for CDRL2, SEQ ID NO: 13 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 14 for CDRH1, SEQ ID NO: 15 for CDRH2, and SEQ ID NO: 16 for CDRH3;
(ii) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 17 for CDRL1, SEQ ID NO: 18 for CDRL2, SEQ ID NO: 19 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 20 for CDRH1, SEQ ID NO: 21 for CDRH2, and SEQ ID NO: 22 for CDRH3;
(iii) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 23 for CDRL1, SEQ ID NO: 24 for CDRL2, SEQ ID NO: 25 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 26 for CDRH1, SEQ ID NO: 27 for CDRH2, and SEQ ID NO: 28 for CDRH3;
(iv) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 29 for CDRL1, SEQ ID NO: 30 for CDRL2, SEQ ID NO: 31 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 32 for CDRH1, SEQ ID NO: 33 for CDRH2, and SEQ ID NO: 34 for CDRH3; or
(v) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 35 for CDRL1, SEQ ID NO: 36 for CDRL2, SEQ ID NO: 37 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 38 for CDRH1, SEQ ID NO: 39 for CDRH2, and SEQ ID NO: 40 for CDRH3,
according to Kabat numbering,
wherein the anti-EBV antibody is conjugated to a drug, an imaging agent, an enzyme label, or biotin.
2. The anti-EBV antibody of claim 1 , comprising a human IgG1 Fc comprising mutations: G236A; S239D; A330L; and 1332E, according to EU numbering.
3. The anti-EBV antibody of claim 1 , comprising a human IgG1 Fc comprising mutations M428L and N434S, according to EU numbering.
4. The anti-EBV antibody of claim 1 , comprising a thioMab.
5. The anti-EBV antibody of claim 1 , comprising an Fc region having a reduced fucose content or lackinq fucose.
6. The anti-EBV antibody of claim 1 , comprising a polyethylene glycol (PEG)-linkage and/or a human serum albumin (HSA)-linkage.
7. The anti-EBV antibody of claim 1 , wherein the anti-EBV antibody is conjugated to an enzyme label comprising alkaline phosphatase, horseradish peroxidase, or β-galactosidase.
8. An antibody-based binding domain comprising:
(i) a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 2 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 1;
(ii) a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 4 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 3;
(iii) a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 6 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 5;
(iv) a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 8 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 7; or
(v) a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 10 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 9;
wherein the antibody-based binding domain is
(a) a single chain variable fragment (scFv); and/or
(b) conjugated to a drug, an imaging agent, an enzyme label, or biotin.
9. The antibody-based binding domain of claim 8 wherein:
(i) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 2 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 1;
(ii) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 4 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 3;
(iii) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 6 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 5;
(iv) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 8 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 7; or
(v) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 10 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 9.
10. The antibody-based binding domain of claim 9 , wherein
(i) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 1 comprises a Q1N mutation;
(ii) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 3 comprises a Q1N mutation;
(iii) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 5 comprises a E1N mutation;
(iv) the variable light chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 6 comprises a Q1N mutation;
(v) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 7 comprises a Q1N mutation;
(vi) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 9 comprises a E1N mutation; and/or
(vii) the variable light chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 10 comprises a E1N mutation.
11. The antibody-based binding domain of claim 8 wherein:
(i) the variable light chain has the sequence as set forth in SEQ ID NO: 2 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 1;
(ii) the variable light chain has the sequence as set forth in SEQ ID NO: 4 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 3;
(iii) the variable light chain has the sequence as set forth in SEQ ID NO: 6 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 5;
(iv) the variable light chain has the sequence as set forth in SEQ ID NO: 8 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 7; or
(v) the variable light chain has the sequence as set forth in SEQ ID NO: 10 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 9.
12. The antibody-based binding domain of claim 8 , comprising a thioMab.
13. The antibody-based binding domain of claim 8 , comprising a polyethylene glycol (PEG)-linkage and/or a human serum albumin (HSA)-linkage.
14. The antibody-based binding domain of claim 8 , wherein the antibody-based binding domain is conjugated to an enzyme label comprising alkaline phosphatase, horseradish peroxidase, or β-galactosidase.
15. An isolated cell transfected with a heterologous nucleic acid encoding
an anti-EBV antibody comprising:
(i) variable light chain complementary determining regions (CDRs) having the sequences as set forth in SEQ ID NO: 11 for CDRL1, SEQ ID NO: 12 for CDRL2, SEQ ID NO: 13 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 14 for CDRH1, SEQ ID NO: 15 for CDRH2, and SEQ ID NO: 16 for CDRH3, according to Kabat numbering; and/or a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 2 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 1;
(ii) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 17 for CDRL1, SEQ ID NO: 18 for CDRL2, SEQ ID NO: 19 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 20 for CDRH1, SEQ ID NO: 21 for CDRH2, and SEQ ID NO: 22 for CDRH3, according to Kabat numbering; and/or
a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 4 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 3;
(iii) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 23 for CDRL1, SEQ ID NO: 24 for CDRL2, SEQ ID NO: 25 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 26 for CDRH1, SEQ ID NO: 27 for CDRH2, and SEQ ID NO: 28 for CDRH3, according to Kabat numbering; and/or
a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 6 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 5;
(iv) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 29 for CDRL1, SEQ ID NO: 30 for CDRL2, SEQ ID NO: 31 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 32 for CDRH1, SEQ ID NO: 33 for CDRH2, and SEQ ID NO: 34 for CDRH3, according to Kabat numbering; and/or
a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 8 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 7;
or
(v) variable light chain CDRs having the sequences as set forth in SEQ ID NO: 35 for CDRL1, SEQ ID NO: 36 for CDRL2, SEQ ID NO: 37 for CDRL3, and variable heavy chain CDRs having the sequences as set forth in SEQ ID NO: 38 for CDRH1, SEQ ID NO: 39 for CDRH2, and SEQ ID NO: 40 for CDRH3, according to Kabat numbering; and/or
a variable light chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 10 and a variable heavy chain having at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 9.
16. The cell of claim 15 , wherein
(i) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 2 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 1;
(ii) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 4 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 3;
(iii) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 6 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 5;
(iv) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 8 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 7; or
(v) the variable light chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 10 and the variable heavy chain has at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 9.
17. The cell of claim 16 , wherein
(i) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 1 comprises a Q1N mutation;
(ii) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 3 comprises a Q1N mutation;
(iii) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 5 comprises a E1N mutation;
(iv) the variable light chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 6 comprises a Q1N mutation;
(v) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 7 comprises a Q1N mutation;
(vi) the variable heavy chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 9 comprises a E1N mutation; and/or
(vii) the variable light chain having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 10 comprises a E1N mutation.
18. The cell of claim 15 , wherein
(i) the variable light chain has the sequence as set forth in SEQ ID NO: 2 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 1;
(ii) the variable light chain has the sequence as set forth in SEQ ID NO: 4 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 3;
(iii) the variable light chain has the sequence as set forth in SEQ ID NO: 6 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 5;
(iv) the variable light chain has the sequence as set forth in SEQ ID NO: 8 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 7; or
(v) the variable light chain has the sequence as set forth in SEQ ID NO: 10 and the variable heavy chain has the sequence as set forth in SEQ ID NO: 9.
19. The cell of claim 16 , wherein the cell is a B cell, a bacterial cell, a mammalian cell, or an insect cell.
20. The cell of claim 16 , further comprising a gene editing nuclease and/or viral vector.