Chlamydia vaccine based on targeting of MOMP VS4 antigen to antigen-presenting cells

Abstract

Chlamydiae are intracellular pathogenic microorganisms that cause a variety of infectious diseases. We have generated antibodies directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells), whose heavy and / or light chains are expressed as antibodies against Chlamydia trachomatis ( Chlamydia trachoma ) is conjugated to the MOMP VS4 domain.

Claims

1. An antibody directed at a surface antigen of an antigen-presenting cell, wherein the heavy chain and / or light chain are conjugated or fused to a VS4 polypeptide having at least 95% identity with the amino acid sequence in the range of amino acid residues from amino acid residue 282 to amino acid residue 358 of SEQ ID NO:

1.

2. The antibody according to claim 1, wherein the heavy chain of the antibody is conjugated or fused to the VS4 polypeptide having at least 95% identity with the amino acid sequence in the range of amino acid residues from amino acid residue 282 to amino acid residue 358 of SEQ ID NO:

1.

3. The antibody according to claim 1, wherein the light chain of the antibody is conjugated or fused to the VS4 polypeptide having at least 95% identity with the amino acid sequence in the range of amino acid residues from amino acid residue 282 to amino acid residue 358 of SEQ ID NO:

1.

4. The antibody according to claim 1, wherein both the heavy chain and light chain of the antibody are conjugated or fused to the VS4 polypeptide having at least 95% identity with the amino acid sequence in the range of amino acid residues from amino acid residue 282 to amino acid residue 358 of SEQ ID NO:

1.

5. The antibody according to any one of claims 1 to 4, wherein the VS4 polypeptide comprises an amino acid sequence in the range of amino acid residues from the 282nd to the 358th amino acid residue of SEQ ID NO:

1.

6. The antibody according to claim 1, which is an IgG antibody, preferably an IgG1 or IgG4 antibody, or more preferably an IgG4 antibody.

7. The antibody according to claim 1, which is a chimeric antibody, particularly a chimeric mouse / human antibody or a humanized antibody.

8. The antibody according to claim 1, selected from antibodies that specifically bind to DC immune receptor (DCIR), MHC class I, MHC class II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, mannose receptor, Langerin, DECTIN-1, B7-1, B7-2, IFN-γ receptor and IL-2 receptor, ICAM-1, Fey receptor, LOX-1, and ASPGR.

9. The antibody according to claim 1, which is specific to CD40.

10. • Derived from the 12E12 antibody, ○ Heavy chain containing complementarity-determining regions CDR1H, CDR2H, and CDR3H (CDR1H has the amino acid sequence GTFFSDYYMY (SEQ ID NO: 3), CDR2H has the amino acid sequence YINSGGGSTYYPDTVKG (SEQ ID NO: 4), and CDR3H has the amino acid sequence RGLPFHAMDY (SEQ ID NO: 5)). ○ and light chains containing complementarity-determining regions CDR1L, CDR2L, and CDR3L (CDR1L has the amino acid sequence SASQGISNYLN (SEQ ID NO: 6), CDR2L has the amino acid sequence YTSILHS (SEQ ID NO: 7), and CDR3L has the amino acid sequence QQFNKLPPT (SEQ ID NO: 8)), - Or derived from 11B6 antibody, ○ Heavy chains containing complementarity-determining regions CDR1H, CDR2H, and CDR3H (CDR1H has the amino acid sequence GYSFTGYYMH (SEQ ID NO: 9), CDR2H has the amino acid sequence RINPYNGATSYNQNFKD (SEQ ID NO: 10), and CDR3H has the amino acid sequence EDYVY (SEQ ID NO: 11)), ○Includes light chains containing complementarity-determining regions CDR1L, CDR2L, and CDR3L (CDR1L has the amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO: 12), CDR2L has the amino acid sequence KVSNRFS (SEQ ID NO: 13), and CDR3L has the amino acid sequence SQSTHVPWT (SEQ ID NO: 14) - Or derived from 12B4 antibody, ○ Heavy chains containing complementarity-determining regions CDR1H, CDR2H, and CDR3H (CDR1H has the amino acid sequence GYTFTDYVLH (SEQ ID NO: 15), CDR2H has the amino acid sequence YINPYNDGTKYNEKFKG (SEQ ID NO: 16), and CDR3H has the amino acid sequence GYPAYSGYAMDY (SEQ ID NO: 17)), ○Includes a light chain containing complementarity-determining regions CDR1L, CDR2L, and CDR3L (CDR1L has the amino acid sequence RASQDISNYLN (SEQ ID NO: 18), CDR2L has the amino acid sequence YTSRLHS (SEQ ID NO: 19), and CDR3L has the amino acid sequence HHGNTLPWT (SEQ ID NO: 20) The antibody according to claim 9.

11. The antibody according to claim 9, wherein the antibody specific to CD40 is selected from the group consisting of mAb1 including the heavy chain variable region of SEQ ID NO: 21 and the light chain variable region of SEQ ID NO: 22, mAb2 including the heavy chain variable region of SEQ ID NO: 23 and the light chain variable region of SEQ ID NO: 22, mAb3 including the heavy chain variable region of SEQ ID NO: 24 and the light chain variable region of SEQ ID NO: 25, mAb4 including the heavy chain variable region of SEQ ID NO: 26 and the light chain variable region of SEQ ID NO: 27, mAb5 including the heavy chain variable region of SEQ ID NO: 28 and the light chain variable region of SEQ ID NO: 29, and mAb6 including the heavy chain variable region of SEQ ID NO: 30 and the light chain variable region of SEQ ID NO:

31.

12. The antibody according to claim 9, which is a CD40 agonist antibody.

13. The antibody according to claim 12, wherein the heavy or light chain of the CD40 agonist antibody (i.e., the chain not conjugated or fused to the VS4 polypeptide) is conjugated or fused to the CD40 binding domain of CD40L (SEQ ID NO: 2).

14. The antibody according to claim 13, wherein the CD40-binding domain of the CD40L is fused to the C-terminus of the light or heavy chain of the CD40 agonist antibody, optionally via a linker, preferably a FlexV1 linker.

15. The antibody according to claim 13, wherein the heavy chain of the antibody is fused to or conjugated to the VS4 polypeptide, and the light chain is conjugated to the CD40 binding domain (SEQ ID NO: 2) of the CD40L.

16. The antibody according to claim 1, which is specific to Langerin.

17. - A heavy chain containing the complementarity-determining regions CDR1H, CDR2H, and CDR3H of the 15B10 antibody, and a light chain containing the complementarity-determining regions CDR1L, CDR2L, and CDR3L of the 15B10 antibody, or - A heavy chain containing the complementarity-determining regions CDR1H, CDR2H, and CDR3H of the 2G3 antibody, and a light chain containing the complementarity-determining regions CDR1L, CDR2L, and CDR3L of the 2G3 antibody, or The antibody according to claim 16, comprising a heavy chain containing complementarity-determining regions CDR1H, CDR2H, and CDR3H of the 4C7 antibody, and a light chain containing complementarity-determining regions CDR1L, CDR2L, and CDR3L of the 4C7 antibody.

18. The antibody according to claim 16, selected from the group consisting of mAb7 including the heavy chain variable region of SEQ ID NO: 32 and the light chain variable region of SEQ ID NO: 33, mAb8 including the heavy chain variable region of SEQ ID NO: 34 and the light chain variable region of SEQ ID NO: 35, and mAb9 including the heavy chain variable region of SEQ ID NO: 36 and the light chain variable region of SEQ ID NO:

37.

19. The antibody according to claim 1, wherein the heavy chain and / or the light chain are fused to the VS4 polypeptide via a linker selected from the group consisting of FlexV1, f1, f2, f3, and f4.

20. i) The antibody according to claim 1, comprising a heavy chain or light chain conjugated via a docklin domain to a cohesin fusion protein consisting of the amino acid sequence defined in SEQ ID NO:

38.

21. The antibody according to claim 10, comprising a heavy chain as defined in SEQ ID NO: 44 and a light chain having the amino acid sequence as defined in SEQ ID NO:

45.

22. A nucleic acid encoding the heavy chain and / or light chain of an antibody according to any one of claims 1 to 21.

23. A vector comprising the nucleic acid described in claim 22.

24. A host cell transfected, infected, or transformed with the nucleic acid described in claim 22 and / or the vector described in claim 23.

25. A vaccine composition comprising the antibody described in any one of claims 1 to 21.

26. A pharmaceutical composition for preventing Chlamydia trachomatis infection, comprising a therapeutically effective amount of the antibody described in any one of claims 1 to 21.

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