Shigella-derived vector and methods of using the same

Patent metadata

Field	Value
Publication number	US-9434772-B2
Application number	US-201214346408-A
Country	US
Kind code	B2
Filing date	Sep 13, 2012
Priority date	Sep 22, 2011
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

Recombinant vectors comprising the cell entry region of the Shigella ox EIEC invasion plasmid are provided, as well as, Shigella or EIEC strains comprising the recombinant vectors. The vectors provide an improved platform for developing attenuated vaccine strains of Shigella or EiEC and for delivering other foreign proteins of interest. The recombinant vectors and bacterial strains comprising the same may be used in methods of inducing an immune response.

First claim

What is claimed:

1. A recombinant vector comprising a cell entry region from a Shigella invasion plasmid and a virF gene from a Shigella invasion plasmid,
wherein the recombinant vector has no more than about 30-50 kilobase pairs of a Shigella invasion plasmid, and
wherein the cell entry region comprises an ipa gene locus, an ipg gene locus, a virB gene, and a mxi-spa gene locus.

2. The recombinant vector of claim 1 , further comprising a selection gene.

3. The recombinant vector of claim 1 , further comprising a virG(icsA) gene from a Shigella bacterium.

4. The recombinant vector of claim 1 , wherein the vector does not contain an osp gene from a Shigella invasion plasmid.

5. The recombinant vector of claim 1 , wherein the vector has no more than about 40-100 kilobase pairs.

6. The recombinant vector of claim 1 , further comprising a nucleic acid encoding a Shigella protein, or a portion thereof, wherein the Shigella protein is not encoded by an ipa gene locus, an ipg gene locus, a virB gene, a mxi-spa gene locus, a virF gene, or a virG(icsA) gene.

7. The recombinant vector of claim 1 , wherein the Shigella cell-entry region is from a Shigella flexneri bacterium.

8. The recombinant vector of claim 1 , further comprising a low copy origin of replication and a high copy origin of replication.

9. The recombinant vector of claim 2 , wherein the selection gene is an antibiotic resistance gene.

10. The recombinant vector of claim 1 , further comprising a nucleic acid encoding a bacterial, viral, fungal, parasitic, or mammalian protein or a portion thereof.

11. A Shigella or E. coli bacterium comprising the recombinant vector of claim 1 , wherein the Shigella or E. coli bacterium is a plasmid-cured bacterium.

12. A Shigella or E. coli bacterium comprising the recombinant vector of claim 10 , wherein the Shigella or E. coli bacterium is a plasmid-cured bacterium.

13. A composition comprising the Shigella or E. coli bacterium of claim 11 and a pharmaceutically acceptable excipient.

14. The composition of claim 13 , further comprising an adjuvant.

15. A composition comprising the Shigella or E. coli bacterium of claim 12 and a pharmaceutically acceptable excipient.

16. The composition of claim 15 , further comprising an adjuvant.

17. A method of inducing an immune response to Shigella in a subject, the method comprising administering the composition of claim 13 to the subject in an amount sufficient to induce an immune response to Shigella in the subject.

Assignees

• Maurelli Anthony T
• Henry M Jackson Found Advancement Military Medicine Inc

Inventors

• Maurelli Anthony T

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/10

  Antimycotics · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61P31/12

  Antivirals · CPC title