Synthetic antigen constructs against Campylobacter jejuni

Patent metadata

Field	Value
Publication number	US-10500262-B2
Application number	US-201815891426-A
Country	US
Kind code	B2
Filing date	Feb 8, 2018
Priority date	Nov 5, 2014
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

The invention relates to immunogenic synthetic constructs capable of inducing an immune response against Campylobacter jejuni (C. jejuni) in a subject comprising one or more monosaccharides comprising one or more MeOPN moieties. Specifically, the invention relates to immunogenic synthetic constructs capable of inducing an immune response against Campylobacter jejuni (C. jejuni) in a subject comprising one or more MeOPN→6 Gal monosaccharides. The invention also relates to compositions comprising the immunogenic synthetic constructs and methods of inducing an immune response against C. jejuni in a subject comprising administering the immunogenic synthetic constructs, and/or compositions comprising the immunogenic synthetic construct, to the subject.

First claim

What is claimed is:

1. An immunogenic synthetic construct capable of inducing an immune response against Campylobacter jejuni ( C. jejuni ) in a subject, wherein said immunogenic synthetic construct comprises one or more MeOPN-6-Gal monosaccharides and one or more MeOPN-2-Gal monosaccharides.

2. The immunogenic synthetic construct of claim 1 wherein the immunogenic synthetic construct is conjugated to a carrier protein.

3. The immunogenic synthetic construct of claim 2 wherein the carrier protein contains at least one T-cell epitope.

4. The immunogenic synthetic construct of claim 2 wherein the carrier protein is an ETEC protein or CRM 197 .

5. The immunogenic synthetic construct of claim 1 further comprising one or more additional saccharides.

6. The immunogenic synthetic construct of claim 5 wherein the one or more additional saccharides is selected from the group consisting of monosaccharides containing one or more MeOPN moieties, galactose, fructose, glucose, heptose, N-acetyl galactosamine, N-acetyl glucosamine, glucitol, glucose, and modified forms of derivatives thereof.

7. The immunogenic synthetic construct of claim 6 wherein said monosaccharide containing one or more MeOPN moieties is MeOPN-1-Fru.

8. The immunogenic synthetic construct of claim 5 wherein said one or more additional saccharides is selected from the group consisting of CPS repeating blocks, heptose units, and MeOPN linkages of C. jejuni serotype complexes HS1, HS3, HS4, and HS23/36.

9. The immunogenic synthetic construct of claim 8 wherein said MeOPN linkages of C. jejuni serotype complexes HS1, HS3, HS4, and HS23/36 are selected from the group consisting of

of HS 1;

of HS4;

of HS23/36.

10. A composition comprising the immunogenic synthetic construct of claim 1 .

11. The composition of claim 10 wherein said composition is a pharmaceutical composition.

12. The composition of claim 11 wherein said pharmaceutical composition is a vaccine.

13. The composition of claim 12 wherein said vaccine is a monovalent vaccine or a polyvalent vaccine.

14. The composition of claim 13 wherein said polyvalent vaccine comprises a formulation against one or more strains of C. jejuni.

15. The composition of claim 14 wherein said polyvalent vaccine further comprises a formulation against enterotoxigenic Escherichia coli (ETEC) or Shigella.

16. The composition of claim 14 wherein said one or more strains of C. jejuni is selected from the group consisting of C. jejuni serotypes HS 23/36, HS 1, HS2, HS3, HS4, and HS5/31.

17. The composition of claim 12 wherein said vaccine further comprises an additional immunoregulatory agent.

18. The composition of claim 17 wherein the additional immunoregulatory agent is selected from the group consisting of antigens of one or more strains of C. jejuni , antigens of enterotoxigenic Escherichia coli (ETEC), Shigella lipopolysaccharide structures, and unconjugated carrier proteins.

19. The composition of claim 12 wherein said vaccine further comprises one or more adjuvants.

20. The composition of claim 19 wherein said adjuvant is selected from the group consisting of toll-like receptor ligands, aluminum phosphate, aluminum hydroxide, monophosphoryl lipid A, liposomes, saponins, QS-21, and derivatives and combinations thereof.

21. A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the immunogenic synthetic construct of claim 1 .

22. The method of claim 21 wherein the subject is human.

23. A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the composition of claim 11 .

24. The method of claim 23 wherein the subject is human.

25. A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the composition of claim 12 .

26. The method of claim 25 wherein said subject is a human.

27. A method of inducing an immune response against C. jejuni in a subject comprising administering to the subject an effective amount of the composition of claim 20 .

28. The method of claim 27 wherein said subject is a human.

29. A method of inducing an immune response against C. jejuni in a subject, said method comprising
(a.) administering to the subject an effective amount of the immunogenic synthetic construct of claim 1 ; and
(b.) optionally administering to the subject one or more boosting doses of the immunogenic synthetic construct administered in step (a).

30. The method of claim 29 wherein the effective amount administered in step (a) is from about 0.1 μg to about 10 mg of the immunogenic synthetic construct.

31. The method of claim 29 wherein said method further comprises administering an adjuvant with the construct in step (a) and/or step (b).

32. The method of claim 31 wherein the adjuvant is selected from the group consisting of toll-like receptor ligands, aluminum phosphate, aluminum hydroxide, monophosphoryl lipid A, liposomes, saponins, QS-21, and derivatives and combinations thereof.

33. A method of inducing an immune response against C. jejuni in a subject, said method comprising
(a). administering to the subject an effective amount of the composition of claim 12 ; and
(b). optionally administering to the subject one or more boosting doses of the composition administered in step (a).

34. The method of claim 33 wherein the effective amount administered in step (a) is from about 0.1 μg to about 10 mg of immunogenic synthetic construct.

35. The method of claim 34 wherein said method further comprises administering an adjuvant with the construct in step (a) and/or step (b).

36. The method of claim 35 wherein the adjuvant is selected from the group consisting of toll-like receptor ligands, aluminum phosphate, aluminum hydroxide, monophosphoryl lipid A, liposomes, saponins, QS-21, and derivatives and combinations thereof.

Assignees

• Us Navy

Inventors

• Guerry Patricia
• Monteiro Mario Artur
• Jiao Yuening

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title