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

Patent metadata

Field	Value
Publication number	US-12076385-B2
Application number	US-202217934781-A
Country	US
Kind code	B2
Filing date	Sep 23, 2022
Priority date	Aug 24, 2015
Publication date	Sep 3, 2024
Grant date	Sep 3, 2024

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 an E. coli O25B antigen polysaccharide at a first concentration, and E. coli O1A, O2 and O6A antigen polysaccharides each at a concentration that is independently 40% or 50% of the first concentration, each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a carrier protein, and the first concentration is 8 to 48 μg/ml.

2. The composition of claim 1 , wherein each of the E. coli O1A, O2 and O6A antigen polysaccharides have the same concentration.

3. The composition of claim 1 , wherein each of the E. coli O1A, O2 and O6A antigen polysaccharides have different concentrations.

4. The composition of claim 1 , comprising 16 μg/ml of the O25B antigen polysaccharide.

5. The composition of claim 1 , comprising 32 μg/m 1 of the O25B antigen polysaccharide.

6. The composition of claim 1 , wherein the first concentration is 10 to 36 μg/ml.

7. A multivalent immune composition comprising an E. coli O25B antigen polysaccharide at a first dose of 5 to 18 μg, and an E. coli O1A antigen polysaccharide, an E. coli O2 antigen polysaccharide and an E. coli O6A antigen polysaccharide each at a dose that is independently 40% or 50% of the first dose, wherein each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a carrier protein.

8. The multivalent immune composition of claim 7 , wherein the E. coli O25B antigen polysaccharide comprises the structure of Formula O25B′:

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

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

and
the E. coli O6A antigen polysaccharide comprises 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.

9. The multivalent immune composition of claim 8 , wherein the first dose is 16 μg.

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

11. The method of claim 10 , wherein the subject is a human.

12. 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, each of the E. coli O1A, O2 and O6A antigens is administered at an effective amount that is independently 40% or 50% of the first effective amount of the E. coli O25B antigen, each of the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are independently covalently bound to a carrier protein, and the first effective amount is 5 to 18 per administration, wherein said subject is a human.

13. The method of claim 12 , wherein 8 μg of the O25B antigen polysaccharide is administered per administration.

14. The method of claim 12 , wherein 16 μg of the O25B antigen polysaccharide is administered per administration.

15. The method of claim 12 , wherein the E. coli O25B, O1A, O2 and O6A antigen polysaccharides are administered together in one composition.

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

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

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

and
the E. coli O6A antigen polysaccharide comprises 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.

17. The method of claim 12 , wherein the immune response limits the severity of or prevents an invasive ExPEC disease caused by ExPEC serotypes O1A, O2 and O6A and O25B in an at-risk human subject.

18. The method of claim 17 , wherein the at-risk human subject has or is at risk of having an invasive ExPEC disease 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.

19. The method of claim 17 , wherein each of the E. coli O1A, O2 and O6A antigens is administered at an effective amount that is 50% of the first effective amount of the E. coli O25B antigen.

20. A process of making a composition of claim 2 , 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.

21. The composition of claim 8 , wherein the composition further comprises at least one additional E. coli O antigen selected from E. coli 04, 07, 08, 015, 016, 018, 021, 073, 075 and 0153 antigens.

22. The method of claim 12 , wherein the composition further comprises at least one additional E.coli O antigen selected from E. coli 04, 07, 08, 015, 016, 018, 021, 073, 075 and 0153 antigens.

Assignees

• Glaxosmithkline Biologicals Sa
• Janssen Pharmaceuticals Inc
• Glaxossmithkline Biologicals 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
• Fonck Veronica Gambillara
• Mally Manuela

Classifications

• A61K39/385

  Haptens or antigens, bound to carriers · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title

• C08B37/0063

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