Methods and compositions for immune protection against extra-intestinal pathogenic E. coli

Patent metadata

Field	Value
Publication number	US-10583185-B2
Application number	US-201615754867-A
Country	US
Kind code	B2
Filing date	Aug 24, 2016
Priority date	Aug 24, 2015
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

Compositions and methods are described for inducing an immune response against extra-intestinal pathogenic Escherichia coli (ExPEC) to thereby provide immune protection against diseases associated with ExPEC. In particular, compositions and methods are described for using conjugates of E. coli polysaccharide antigens O25B, O1A, O2, and O6A covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein as vaccines for the prevention of invasive ExPEC disease caused by ExPEC serotypes O1A, O2, O6A and O25B.

First claim

What is claimed is:

1. A composition comprising a first concentration of an E. coli O 25B antigen polysaccharide, and a second concentration of each of an E. coli O1A antigen polysaccharide, an E. coli O2 antigen polysaccharide and an E. coli O6A antigen polysaccharide, wherein the ratio of the first concentration to the second concentration is 2:1, each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein, and the first concentration is 10 to 36 μg/ml.

2. The composition of claim 1 , comprising the E. coli O25B, O1A, O2 and O6A antigen polysaccharides at a weight ratio of 2:1:1:1, wherein the first concentration is 10, 16, 24, 32 or 36 μg/ml.

3. The composition of claim 1 , comprising 16 μg/ml of the E. coli O 25B antigen polysaccharide.

4. The composition of claim 1 , comprising 32 μg/ml of the E. coli O 25B antigen polysaccharide.

5. A multivalent immune composition comprising an E. coli O25B antigen polysaccharide having the structure of Formula O25B′:

an E. coli O1A antigen polysaccharide having the structure of Formula O1A′:

an E. coli O2 antigen polysaccharide having the structure of Formula O2′:

and
an E. coli O6A antigen polysaccharide having the structure of Formula O6A′:

wherein n is independently an integer of 5 to 25, and
each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a carrier protein having the amino acid sequence of SEQ ID NO:1; and
the concentrations of the E. coli O25B, O1A, O2, O6A antigen polysaccharides in the composition are respectively 16:8:8:8 μg/ml or 32:16:16:16 μg/ml.

6. A method of inducing an immune response to extra-intestinal pathogenic E. coli (ExPEC) in a subject, comprising administering to the subject the composition of claim 1 .

7. A method of inducing an immune response to extra-intestinal pathogenic E. coli (ExPEC) in a subject, comprising administering to the subject a first effective amount of an E. coli O25B antigen polysaccharide, and a second effective amount of each of an E. coli O1A antigen polysaccharide, an E. coli O2 antigen polysaccharide and an E. coli O6A antigen polysaccharide, wherein the ratio of the first effective amount to the second effective amount is 2:1, each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein, and the first effective amount is 5 to 18 μg per administration.

8. The method of claim 7 , wherein the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are administered at a dosage ratio of 2:1:1:1, wherein the first effective amount is 6, 8, 10, 12, 14, 16, or 18 μg per administration.

9. The method of claim 7 , wherein 8 μg of the E. coli O25B antigen polysaccharide is administered per administration.

10. The method of claim 7 , wherein 16 μg of the E. coli O25B antigen polysaccharide is administered per administration.

11. The method of claim 7 , wherein the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are administered together in one composition.

12. The method of claim 7 , wherein the E. coli O25B antigen polysaccharide has the structure of Formula O25B′:

the E. coli O1A antigen polysaccharide has the structure of Formula O1A′:

the E. coli O2 antigen polysaccharide has the structure of Formula O2′:

and
the E. coli O6A antigen polysaccharide has the structure of Formula O6A′:

wherein n is independently an integer of 5 to 25,
each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a carrier protein having the amino acid sequence of SEQ ID NO:1, and the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are administered at 8:4:4:4 μg or 16:8:8:8 μg per administration.

13. The method of claim 6 , wherein the subject has or is at risk of having an invasive ExPEC disease.

14. The method of claim 13 , wherein invasive ExPEC disease is selected from the group consisting of urinary tract infection, a surgical-site infection, an abdominal or pelvic infection, pneumonia, nosocomial pneumonia, osteomyelitis, cellulitis, sepsis, bacteremia, a wound infection, pyelonephritis, meningitis, neonatal meningitis, peritonitis, cholangitis, soft-tissue infections, pyomyositis and septic arthritis.

15. A method of inducing an immune response to extra-intestinal pathogenic E. coli (ExPEC) in a subject, comprising administering to the subject the multivalent immune composition of claim 5 .

16. The method of claim 15 , wherein the subject has or is at risk of having an invasive ExPEC disease.

17. A process of making the composition of claim 1 , comprising combining the E. coli O25B antigen polysaccharide, the E. coli O1A antigen polysaccharide, the E. coli O2 antigen polysaccharide and the E. coli O6A antigen polysaccharide to thereby obtain the composition, wherein each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides is independently covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein.

18. A process of making the multivalent immune composition of claim 5 , comprising combining the E. coli O25B antigen polysaccharide, the E. coli O1A antigen polysaccharide, the E. coli O2 antigen polysaccharide and the E. coli O6A antigen polysaccharide to thereby obtain the multivalent immune composition, wherein each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides is independently covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein.

19. The composition of claim 1 , wherein each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides independently covalently bound to the carrier protein is a bioconjugate.

20. The multivalent immune composition of claim 5 , wherein each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides independently covalently bound to the carrier protein is a bioconjugate.

Assignees

• Glaxosmithkline Biologicals Sa
• Janssen Pharmaceuticals Inc
• Glaxosmithkline Biological S A

Inventors

• Poolman Jan Theunis
• Jacquemyn Bert
• Abbanat Darren Robert
• Yon Patricia Ibarra
• Hermans Peter Wilhelmus Maria
• Kowarik Michael Thomas
• Wetter Michael Lukas
• Kemmler Stefan Jochen
• Häuptle Micha Andres
• Gambillara Fonck Veronica
• Mally Manuela

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• C08B37/0063

  Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan · CPC title

• A61K2039/55583

  Polysaccharides · CPC title

• A61K39/0258 Primary

  Escherichia · CPC title