Attenuated salmonella SP12 mutants as antigen carriers

1. An isolated attenuated Salmonella cell comprising the SPI2 gene locus, wherein at least one secretion apparatus (ssa) gene selected from the group consisting of ssaB, ssaC, ssaD, ssaE, ssaG, ssaH, ssaI, ssaJ, ssaP, ssaT, and ssaV of the SPI2 locus is inactivated, wherein said inactivation results in an attenuation/reduction of virulence compared to the wild type of said cell and wherein at least one additional gene located outside the SPI2 locus is inactivated, wherein the inactivation results in further attenuation/reduction of virulence compared to the wild type.

2. The isolated attenuated Salmonella cell of claim 1 wherein said additional gene is an aro gene.

3. The isolated attenuated Salmonella cell of claim 2 wherein the aro gene is aroA.

4. The isolated attenuated Salmonella cell of claim 1 wherein inactivation of said gene is effected by a deletion or an insertion or a combination of deletion and insertion.

5. The isolated attenuated Salmonella cell of claim 1 wherein the Salmonella is S. typhimurium or S. typhi.

6. The isolated attenuated Salmonella cell of claim 1 , wherein said Salmonella cell is capable of presenting antigen to a host, wherein said cell comprises at least one heterologous nucleic acid molecule comprising a nucleic acid sequence coding for said antigen, wherein said cell is capable of expressing said nucleic acid molecule.

7. The isolated attenuated Salmonella cell of claim 6 , wherein the nucleic acid sequence coding for said antigen is in a gene expression cassette.

8. The isolated attenuated Salmonella cell of claim 6 , wherein the nucleic acid sequence coding for said antigen is under the control of a Salmonella promoter.

9. The isolated attenuated Salmonella cell of claim 7 , wherein said gene expression cassette further comprises an accessory sequence for secretion of the antigen.

10. The isolated attenuated Salmonella cell of claim 6 , wherein the antigen is a bacterial, viral or tumor antigen.

11. The isolated attenuated Salmonella cell of claim 10 , wherein the antigen is selected from the group consisting of an antigen from a hepatitis virus, an antigen from a human papillomavirus, an antigen from a herpes virus, an antigen from Helicobacter pylori , an antigen from Chlamydia pneumoniae , an antigen from Borrellia burgdorferi , and an antigen from a Nanobacteria.

12. The isolated attenuated Salmonella cell of claim 6 wherein the nucleic acid sequence coding for the antigen is fused to a nucleic acid sequence encoding an immunologically reactive protein.

13. The isolated attenuated Salmonella cell of claim 6 , wherein the heterologous nucleic acid molecule is inserted into the SPI2 locus.

14. The isolated attenuated Salmonella cell of claim 1 , wherein said Salmonella cell is useful as a pharmaceutical.

15. A pharmaceutical composition comprising the isolated attenuated Salmonella cell of claim 1 and a pharmaceutically acceptable diluent, carrier and/or adjuvant.

16. The isolated attenuated Salmonella cell of claim 1 , wherein said Salmonella cell is useful in the preventive or therapeutic treatment of a disease caused by Salmonella.

17. The isolated attenuated Salmonella cell of claim 10 , wherein antigen is a bacterial antigen, and wherein said Salmonella cell is useful in the prevention or therapeutic treatment of a bacterial infection.

18. The isolated attenuated Salmonella cell of claim 6 , wherein the Salmonella cell is useful in presenting an antigen to a host.