Vaccines against
The present invention describes an efficient vaccine against a Chlamydia trachomatis (Ct). The vaccine is based on recombinant fusion molecules that are capable of generating a high titered neutralizing antibody response that is protective against various Ct serovars. Our invention furthermore describe the combination of these antibody promoting fragments with Ct antigens that are targets for T cells with the aim to provide a vaccine that activate both arms of the immune system.
1 . A nucleic acid encoding a polypeptide comprising 3 or more immuno-repeat units of surface exposed fragments of a Chlamydia major outer membrane protein (MOMP), each of said immune-repeat units comprising an amino acid sequence from a variable domain 4 (VD4) region selected from:
VD4-SvD (SEQ ID NO: 15);
VD4-SvE (SEQ ID NO: 16);
VD4-SvF (SEQ ID NO: 17);
VD4-Svla (SEQ ID NO: 18);
VD4-SvG (SEQ ID NO: 19);
VD4-SvJ (SEQ ID NO: 20);
VD4 ext SvD (SEQ ID NO: 23);
VD4 ext SvE (SEQ ID NO: 24);
VD4 ext SvF (SEQ ID NO: 25);
VD4 ext SvG (SEQ ID NO: 26);
VD4 ext Svla (SEQ ID NO: 27);
VD4 ext SvJ (SEQ ID NO: 28), wherein each of said at least 3 or more immuno-repeat units is from a different serovar, wherein optionally the cysteine residue in SEQ ID Nos: 17-18, 25-26 is substituted with serine to prevent formation of a disulfide bond.
2 . The nucleic acid according to claim 1 , wherein said polypeptide further comprises at least one immuno-repeat amino acid sequence from a variable domain 1 (VD1) region selected from:
VD1-SvD (SEQ ID NO: 1);
VD1-SvE (SEQ ID NO: 2);
VD1-SvF (SEQ ID NO: 3);
VD1-Svla (SEQ ID NO: 4);
VD1-SvG (SEQ ID NO: 5);
VD1-SvJ (SEQ ID NO: 6);
VD1 ext SvD (SEQ ID NO:9);
VD1 ext SVE (SEQ ID NO: 10);
VD1 ext SvF (SEQ ID NO:11);
VD1 ext SvG (SEQ ID NO: 12):
VD1 ext Svla (SEQ ID NO: 13) and
VD1 ext SvJ (SEQ ID NO: 14).
3 . The nucleic acid according to claim 2 , wherein the encoded polypeptide comprises the at least 3 VD4 regions, and the at least one VD1 region of the MOMP placed next to each other.
4 . The nucleic acid of claim 2 , further comprising a linked nucleic acid encoding a moiety that facilitates export of the polypeptide when produced recombinantly, a moiety that facilitates purification of the encoded polypeptide, or a moiety which enhances immunogenicity, wherein said moiety which enhances immunogenicity is a T-cell target selected from Chlamydia trachomatis (Ct) antigens CT043, CT004, CT414, and CT681.
5 . The nucleic acid according to claim 4 , wherein said encoded polypeptide has an amino acid sequence of SEQ ID NO: 60.
6 . A pharmaceutical composition comprising the nucleic acid of claim 5 , and one or more of a pharmacologically acceptable carrier, excipient, adjuvant, and immune modulator, wherein said nucleic acid is DNA or RNA.
7 . The nucleic acid according to claim 1 , wherein the VD4 immuno-repeat units comprise at least serovars D, E and F.
8 . The nucleic acid according to claim 1 , wherein said encoded polypeptide comprises i) an N terminal sequence of SEQ ID NO: 21 or a subsequence thereof, said subsequence comprising 1-38 amino acid residues, starting with the C-terminal K in the amino acid sequence in SEQ ID NO: 21 and
ii) a C-terminal sequence of SEQ ID NO: 22 or a subsequence thereof, said subsequence comprising 1-29 amino acid residues, starting with the N-terminal D in SEQ ID NO: 22.
9 . The nucleic acid according to claim 1 , where said encoded polypeptide comprises the amino acid sequence selected from SEQ ID NO: 46, 47, 48, 53, 54, 55, 60, 64, 65, 66, 67, 69 and 70.
10 . The nucleic acid according to claim 1 , further comprising a linked nucleic acid encoding a moiety that facilitates export of the polypeptide when produced recombinantly, a moiety that facilitates purification of said encoded polypeptide, or a moiety which enhances immunogenicity.
11 . The nucleic acid according to claim 10 , wherein said moiety which enhances immunogenicity is a T-cell target selected from Chlamydia trachomatis (Ct) antigens CT043, CT004, CT414, and CT681.
12 . The nucleic acid according to claim 11 , wherein said encoded polypeptide has an amino acid sequence selected from SEQ ID NO: 64, 65, 66 and 67.
13 . A pharmaceutical composition comprising the nucleic acid of claim 12 and one or more of a pharmacologically acceptable carrier, excipient, adjuvant, and immune modulator, wherein said nucleic acid is DNA or RNA.
14 . A pharmaceutical composition comprising the nucleic acid of claim 12 which encodes a polypeptide of SEQ ID NO: 64 and one or more of a pharmacologically acceptable carrier, excipient, adjuvant, and immune modulator, wherein said nucleic acid is DNA or RNA.
15 . The nucleic acid according to claim 1 , wherein said nucleic acid is DNA or RNA.
16 . A pharmaceutical composition comprising the nucleic acid according to claim 1 and one or more of a pharmacologically acceptable carrier, excipient, adjuvant, and immune modulator, wherein said nucleic acid is DNA or RNA.