Synthetic anti-plague antibodies

1. A monoclonal antibody that specifically binds Yersinia pestis F1 antigen, comprising a variable light (VL) domain and a variable heavy (VH) domain, wherein:

the VL domain comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 sequences of SEQ ID NO: 1 and the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 2; or

the VL domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 3 and the VH domain comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 4.

2. The monoclonal antibody of claim 1 , wherein the CDR sequences are determined using the method of Kabat, IMGT or Chothia.

3. The monoclonal antibody of claim 1 , wherein:

the VL domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 23-33, 49-55 and 88-96 of SEQ ID NO: 1 and the VH domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 26-35, 52-60 and 100-108 of SEQ ID NO: 2; or

the VL domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 24-34, 50-56 and 90-97 of SEQ ID NO: 3 and the VH domain CDR1, CDR2 and CDR3 sequences respectively comprise residues 26-35, 52-59 and 98-104 of SEQ ID NO: 4.

4. The monoclonal antibody of claim 3 , wherein:

the amino acid sequence of the VL domain is at least 90% identical to residues 1-107 of SEQ ID NO: 1 and the amino acid sequence of the VH domain is at least 90% identical to residues 1-119 of SEQ ID NO: 2; or

the amino acid sequence of the VL domain is at least 90% identical to residues 1-106 of SEQ ID NO: 3; and the amino acid sequence of the VH domain is at least 90% identical to residues 1-115 of SEQ ID NO: 4.

5. The monoclonal antibody of claim 4 , wherein:

the amino acid sequence of the VL domain comprises or consists of residues 1-107 of SEQ ID NO: 1 and the amino acid sequence of the VH domain comprises or consists of residues 1-119 of SEQ ID NO: 2; or

the amino acid sequence of the VL domain comprises or consists of residues 1-106 of SEQ ID NO: 3 and the amino acid sequence of the VH domain comprises or consists of residues 1-115 of SEQ ID NO: 4.

6. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is an antigen-binding fragment selected from an Fab fragment, an Fab′ fragment, an F(ab)′ 2 fragment, a single chain variable fragment (scFv) and a disulfide stabilized variable fragment (dsFv).

7. The monoclonal antibody of claim 1 , wherein the antibody is an IgG.

8. The monoclonal antibody of claim 7 , comprising:

a light chain comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 2; or

a light chain comprising the amino acid sequence of SEQ ID NO: 3 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 4.

9. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is a human antibody or a chimeric antibody.

10. An immunoconjugate comprising the monoclonal antibody of claim 1 and an effector molecule.

11. The immunoconjugate of claim 10 , wherein the effector molecule is a detectable label or a radionuclide.

12. The immunoconjugate of claim 11 , wherein the immunoconjugate comprises a chelator and the radionuclide is bound to the chelator.

13. The immunoconjugate of claim 12 , wherein the chelator is diethylene-triamine-pentaacetic acid (DTPA), cyclohexane-diethylene-triamine-pentaacetic-acid (CHX-DTPA), p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA), ethylenediamine-tetraacetic acid (EDTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA), 1,4,7-triazacyclononane-N,N′,N″-triacetetate (NOTA), ethylenediamine tetra(methylene phosphonic acid) (EDTMP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP), N-chloro-p-toluenesulfonamide, tetrachloro-3-6α-diphenylglycouril-3, (2-(4-isothiocyanatobenzyl-1,4,7,10-tetraaza-1,4,7,10,tetra-(2-carbamonyl-methyl)-cyclododecane) (TCMC), tris(hydroxypyridinone) (THP), or desferrioxamine (DFO).

14. The immunoconjugate of claim 12 , wherein the radionuclide is 99m Tc, 123 I, 125 I, 131 I, 111 In, 97 Ru, 64 Cu, 67 Ga, 68 Ga, 72 As, 89 Zr, 90 Y or 201 Tl.

15. A fusion protein, comprising the monoclonal antibody of claim 1 and a heterologous protein or peptide.

16. An isolated nucleic acid molecule encoding the monoclonal antibody of claim 1 .

17. A vector comprising the nucleic acid molecule of claim 16 .

18. A host cell comprising the vector of claim 17 .

19. A composition comprising the monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.

20. A method of treating a Yersinia pestis infection in a subject, comprising administering to the subject a therapeutically effective amount of the monoclonal antibody of claim 1 , thereby treating the Y. pestis infection in the subject.

21. A method of detecting Yersinia pestis in a sample, comprising:

contacting the sample with the monoclonal antibody of claim 1 ; and

detecting binding of the monoclonal antibody to the sample, thereby detecting Y. pestis in the sample.

22. A method of detecting F1 antigen or an F1-expressing Y. pestis in a sample, comprising:

contacting the sample with the monoclonal antibody of claim 1 ; and

detecting binding of the monoclonal antibody to the sample, thereby detecting F1 antigen or F1-expressing Y. pestis in the sample.