Attenuated Salmonella bacteria and methods of using

Patent metadata

Field	Value
Publication number	US-9636386-B2
Application number	US-201414777415-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

Provided herein are attenuated Salmonella bacteria for expressing autoantigen alone or in combination with an immunomodulator, as well as methods of using these bacteria to treat various autoimmune disorders.

First claim

What is claimed is:

1. An attenuated Salmonella bacterium comprising a nucleic acid encoding a diabetic autoantigen selected from the group consisting of proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase, chromogranin A, islet amyloid polypeptide, heat shock protein 60, islet antigen 2, and zinc transporter-8, wherein the nucleic acid encoding the diabetic autoantigen is under the control of an SPI2 promoter.

2. The attenuated Salmonella bacterium of claim 1 , further comprising a nucleic acid encoding an immunomodulator.

3. The attenuated Salmonella bacterium of claim 2 , wherein the immunomodulator is selected from the group consisting of TGFβ, interleukin-10 (IL-10), interleukin-4 (IL-4), and interleukin-27 (IL-27).

4. A pharmaceutical formulation comprising the attenuated Salmonella bacterium of claim 1 and a pharmaceutically acceptable carrier.

5. A method of treating an autoimmune disorder in a subject in need thereof comprising administering:
(a) an attenuated Salmonella bacterium comprising a nucleic acid encoding a diabetic autoantigen selected from the group consisting of proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase, chromogranin A, islet amyloid polypeptide, heat shock protein 60, islet antigen 2, and zinc transporter-8, wherein expression of the diabetic autoantigen is under the control of an SPI2 promoter; and
(b) a vector comprising a nucleic acid encoding an immunomodulator;
wherein administration of the attenuated Salmonella bacterium and the vector comprising a nucleic acid encoding an immunomodulator results in expression of the diabetic autoantigen and the immunomodulator in the subject.

6. A method of treating an autoimmune disorder in a subject in need thereof comprising administering:
(a) an attenuated Salmonella bacterium comprising a nucleic acid encoding a diabetic autoantigen selected from the group consisting of proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase, chromogranin A, islet amyloid polypeptide, heat shock protein 60, islet antigen 2, and zinc transporter-8, wherein expression of the diabetic autoantigen is under the control of an SPI2 promoter, and wherein administration of the attenuated Salmonella bacterium results in expression of the diabetic autoantigen; and
(b) one or more immunomodulators.

7. The method of claim 5 , wherein the immunomodulator is selected from the group consisting of TGFβ, interleukin-10 (IL-10), interleukin-4 (IL-4), and interleukin-27 (IL-27).

8. The method of claim 6 , wherein the immunomodulator is selected from the group consisting of TGFβ, interleukin-10 (IL-10), interleukin-4 (IL-4), and interleukin-27 (IL-27).

9. The method of claim 5 , wherein the vector comprising a nucleic acid encoding an immunomodulator is an attenuated Salmonella bacterium.

10. The method of claim 9 , wherein the same attenuated Salmonella bacterium comprises the nucleic acid encoding the immunomodulator and the nucleic acid encoding the diabetic autoantigen.

11. A vaccine composition comprising an immunologically protective amount of an attenuated Salmonella bacterium of claim 1 , wherein the vaccine composition is formulated in an oral dosage form.

12. The method of claim 5 , wherein the attenuated Salmonella bacterium is administered by oral administration.

13. The method of claim 6 , wherein the attenuated Salmonella bacterium is administered by oral administration.

Assignees

• Husseiny Elsayed Mohamed I
• Ferreri Kevin
• Hope City

Inventors

• Husseiny Elsayed Mohamed I
• Ferreri Kevin

Classifications

• A61K2039/522

  avirulent or attenuated · CPC title

• A61K2039/55516

  Proteins; Peptides · CPC title

• A61K2035/11

  Medicinal preparations comprising living procariotic cells · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K35/74

  Bacteria (therapeutic use of a bacterial protein A61K38/00) · CPC title