Patent
The invention provides an attenuated Salmonella vaccine vector comprising one or more heterologous polynucleotides that encode immunogenic Chlamydial peptides. In one embodiment, the attenuated Salmonella vaccine vector comprises aroC and ssaV attenuating mutations. The heterologous polynucleotides encoding the immunogenic Chlamydial peptides can be under the control of an inducible promoter such as a Salmonella ssaG promoter. In one embodiment of the invention, the immunogenic Chlamydial peptide is a PmpG peptide, for instance, a CT110, CT84 or CT40 peptide.
1. An attenuated Salmonella microorganism comprising i) an attenuating mutation in a Salmonella Pathogenicity Island 2 (SPI-2) gene; ii) an attenuating mutation in a second gene; and iii) one or more gene expression cassettes, each gene expression cassette comprising a heterologous nucleic acid under the control of an inducible promoter, wherein at least one of said heterologous nucleic acid encodes an immunogenic Chlamydial peptide and Wherein the Chlamydial peptide is secreted from the attenuated Salmonella microogranism via a secretion signal.
2. The attenuated Salmonella microorganism of claim 1 , wherein said attenuated Salmonella microorganism induces an effective immune response when administered to a human patient.
3. The attenuated Salmonella microorganism of claim 1 , wherein the second gene is a Salmonella gene involved in the biosynthesis of aromatic compounds.
4. The attenuated Salmonella microorganism of claim 3 , wherein the gene involved in the biosynthesis of aromatic compounds is aroC.
5. The attenuated Salmonella microorganism of claim 1 , wherein the SPI-2 gene is selected from the group consisting of a ssa, sse, ssc or ssr gene.
6. The attenuated Salmonella microorganism of claim 5 , wherein said SPI-2 gene is an ssa gene.
7. The attenuated Salmonella microorganism of claim 6 , wherein said ssa gene is selected from the group consisting of ssaV, ssaJ, ssaU, ssaK, ssaL, ssaM, ssaO, ssaP, ssaQ, ssaR, ssaS, ssaT, ssaU, ssaD, ssaE, ssaG, ssal, ssaC (spiA) and ssaH.
8. The attenuated Salmonella microorganism of claim 7 , wherein said ssa gene is ssaV.
9. The attenuated Salmonella microorganism of claim 7 , wherein said ssa gene is ssaJ.
10. The attenuated Salmonella microorganism of claim 1 , wherein the attenuating mutation in the SPI-2 gene is a deletion or inactivation of the SPI-2 gene, and wherein the attenuating mutation in the second gene is a deletion or inactivation of the second gene.
11. The attenuated Salmonella microorganism of claim 10 , wherein the gene expression cassette is inserted at the SPI-2 gene deletion site and/or the second gene deletion site.
12. The attenuated Salmonella microorganism of claim 11 , wherein the SPI-2 deletion site is an ssaV gene deletion site and the second gene deletion site is an aroC deletion site.
13. The attenuated Salmonella microorganism of claim 1 , wherein said inducible promoter is a Salmonella -ssaG promoter.
14. The attunuated Salmonella microorganism of claim 1 , wherein the immunogenic Chlamydial peptide is selected from the group consisting of PmpG, Pmpl, PmpE, MOMP, PmpD, PmpH, OmcB, OmpH, and HtrA or an immunogenic fragment thereof.
15. The attenuated Salmonella microorganism of claim 14 , wherein said immunogenic Chlamydial peptide is PmpG or an immunogenic fragment thereof.
16. The attenuated Salmonella microorganism of chum 15 , wherein said PmpG or an immunogenic fragment thereof binds to an antibody to PmpG.
17. The attenuated Salmonella microorganism of claim 15 , wherein said PmpG or immunogenic fragment thereof is CT84, CT110 or CT40.
18. The attenuated Salmonella microorganism of claim 1 , wherein the Chlamydial peptide is a C. trachomatis peptide, C. pneumoniae peptide or a C. muridarum peptide.
19. The attenuated Salmonella microorganism of claim 1 , wherein the gene expression cassette further comprises a nucleic acid encoding a linker peptide.
20. A composition for the treatment or prevention of a Chlamydial infection or related condition comprising the attenuated Salmonella microorganism of claim 1 , and a pharmaceutically acceptable carrier and/or diluent.
21. The composition of claim 20 further comprising at least one adjuvant.
22. A method for vaccinating a subject against a Chlamydial infection, comprising: administering the composition of claim 20 to said subject.
23. A method for preventing or ameliorating a condition associated with a Chlamydial infection, comprising: administering the composition of claim 20 to said subject.