Patent
The present invention relates to Salmonella enterica comprising at least one pgl operon of Campylobacter jejuni or a functional derivative thereof and presenting at least one N-glycan of Campylobacter jejuni or N-glycan derivative thereof on its cell surface. In addition, it is directed to medical uses and pharmaceutical compositions thereof as well as methods for treating and/or preventing Campylobacter and optionally Salmonella infections and methods for producing these Salmonella strains.
1. Salmonella enterica , comprising at least one pgl operon of Campylobacter jejuni and further comprising at least one N-glycan of Campylobacter jejuni on its cell surface, wherein one or more genes for bacillosamine biosynthesis are inactivated by mutation or partial or complete deletion.
2. Salmonella enterica of claim 1 selected from the group consisting of Salmonella typhimurium, enteriditis, heidelberg, gallinorum, hadar, agona, kentucky and infantis.
3. Salmonella enterica of claim 2 selected from Salmonella enterica typhimurium strains.
4. Salmonella enterica of claim 1 , wherein the partial and/or complete deletion is of the genes pgl D, E, F.
5. Salmonella enterica of claim 1 , wherein the pglB gene product is inactivated by mutation or deletion.
6. Salmonella enterica according to claim 1 , wherein at least one N-glycan has formula (II) GalNAc-a1,4-GalNAc-a1,4-[Glc-β-1,3]GalNAc-a1,4-Gal-NAc-a1,4-GalNAc-a1,3-GlcNAc.
7. Salmonella enterica according to claim 1 , wherein the N-glycan(s) or derivative(s) is (are) linked to at least one homologous or heterologous Salmonella polypeptide that is (are) transferred to and presented on the cell surface, including but not limited to a linkeage to at least one polypeptide comprising at least one consensus sequon N-Z-S/T, wherein X and Z may be any natural amino acid except Pro.
8. Salmonella enterica according to claim 1 , wherein the at least one N-glycan is linked to the Salmonella lipid A core.
9. Salmonella enterica according to claim 1 , wherein the Salmonella strain is attenuated.
10. Salmonella enterica according to claim 1 , wherein the attenuation occurs by mutations selected from the group consisting of pab, pur, aro, aroA, asd, dap, nadA, pncB, galE, pmi, fur, rpsL, ompR, htrA, hemA, cdt, cya, crp, phoP, phoQ, rfc, poxA and galU, more preferably mutations aroA, cya and crp.
11. Salmonella enterica of claim 1 , wherein the Salmonella strain is attenuated by partial or full inactivation of the expression of the O-antigen.
12. Salmonella enterica of claim 11 , wherein partial or full inactivation of the expression of the 0-antigen occurs by one or more mutations or deletions in the rfb gene cluster, including but not limited to a mutation in or deletion of the wbaP gene.
13. Salmonella enterica of claim 1 , including but not limited to a serovar typhimurium strain, comprising mutations or deletions in the wbaP gene leading to complete inactivation of O-antigen biosynthesis and further comprising on its cell surface at least one N-glycan GalNAc-a1,4-GalNAc-a1,4-[Glc-β-1,3]GalNAc-a1,4-Gal-NAc-a1,4-GalNAc-a1,3-GlcNAc.
14. A pharmaceutical composition, feed, or feed additive comprising Salmonella enterica , including but not limited to live Salmonella enterica , according to claim 1 and optionally physiologically acceptable excipients.