Methods and compositions based on Shiga toxin type 2 protein

Patent metadata

Field	Value
Publication number	US-9801931-B2
Application number	US-201514628667-A
Country	US
Kind code	B2
Filing date	Feb 23, 2015
Priority date	Jan 23, 2009
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The invention is based on the discovery of the epitope in the Stx2 protein for the 11 E1O antibody. The invention features compositions containing non-full length Stx2 polypeptides that include the 11 E1O monoclonal antibody epitope. The invention also features methods of producing anti-Stx2 antibodies specific for the 11 E1O epitope of the Stx2 protein. Additionally, the invention features methods for treating a subject having, or at risk of developing, a Shiga toxin associated disease (e.g., hemolytic uremia syndrome and diseases associated with E. coli and S. dysenteriae infection) with a polypeptide that includes the 11 E1O epitope or with an anti-Stx2 antibody developed using the methods of the invention. Furthermore, the invention features the detection of Stx2 in a sample using the antibodies developed using the methods of the invention.

First claim

What is claimed is:

1. A composition for stimulating an immune response against Stx2 comprising a pharmaceutically acceptable carrier and at least one purified polypeptide, said polypeptide consisting of SEQ ID NO: 1, SEQ ID NO:2, or SEQ ID NO:3 and a non-Stx2 protein scaffold, wherein said SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 is inserted into said non-Stx2 protein scaffold, wherein the amino acid sequence of said non-Stx2 protein scaffold shares at least 75% sequence identity with the amino acid sequence of Stx1 subunit A, and wherein said polypeptide has the antigenicity of Stx2.

2. The composition of claim 1 , wherein said scaffold shares at least 80% identity to Stx1 subunit A.

3. The composition of claim 1 , wherein said composition further comprises an adjuvant.

4. A purified polypeptide consisting of:
SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 and a non-Stx2 protein scaffold, wherein said SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 is inserted into said non-Stx2 protein scaffold, wherein the amino acid sequence of said non-Stx2 protein scaffold shares at least 75% sequence identity with the amino acid sequence of Stx1 subunit A, and wherein said polypeptide has the antigenicity of Stx2.

5. The purified polypeptide of claim 4 , wherein said scaffold shares at least 80% identity to Stx1 subunit A.

6. A composition for stimulating an immune response against Stx2 comprising a pharmaceutically acceptable carrier and at least one purified polypeptide, said polypeptide consisting of:
(i) SEQ ID NO: 1, SEQ ID NO:2, or SEQ ID NO:3; and (ii) a non-Stx2 protein scaffold, wherein said SEQ ID NO: 1, SEQ ID NO:2, or SEQ ID NO:3 is inserted into said non-Stx2 protein scaffold wherein said polypeptide does not include full-length Stx2 polypeptide.

Assignees

• Henry M Jackson Found Advancement Military Medicine Inc

Inventors

• O'Brien Alison D
• Melton-Celsa Angela
• Smith Michael
• Sinclair James

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title