Multiple antigen presenting immunogenic composition, and methods and uses thereof

Patent metadata

Field	Value
Publication number	US-10766932-B2
Application number	US-201214116402-A
Country	US
Kind code	B2
Filing date	May 11, 2012
Priority date	May 11, 2011
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

The present embodiments provide for an immunogenic multiple antigen presenting system comprising a polymer to which antigens are associated by complementary affinity molecules. For example, the polymer can be a polysaccharide, or antigenic polysaccharide, to which protein or peptide antigens from the same or different pathogens are indirectly linked. The present immunogenic compositions can elicit both humoral and cellular immune responses to one or multiple antigens at the same time.

First claim

We claim:

1. An immunogenic composition comprising an immunologically effective amount of at least one antigenic polysaccharide, an immunologically effective amount of one to ten different peptide or polypeptide antigens, and one to ten different pairs of affinity molecules, wherein each pair comprises a first affinity molecule and a second affinity molecule complementary to the first affinity molecule, wherein in each pair:
the first affinity molecule is associated with the at least one antigenic polysaccharide, and
the complementary second affinity molecule is covalently attached to one of the peptide or polypeptide antigens to form a fusion protein, and
the first affinity molecule non-covalently associates with the complementary second affinity molecule to link the respective peptide or polypeptide antigen and the at least one antigenic polysaccharide; and
wherein the immunogenic composition, upon administration to a subject, elicits (i) an immune response to the at least one antigenic polysaccharide, and (ii) an immune response to at least one of the one to ten different peptide or polypeptide antigens, in the subject.

2. The immunogenic composition of claim 1 , wherein the first affinity molecule is cross-linked or covalently bonded to the antigenic polysaccharide.

3. The immunogenic composition of claim 2 , wherein the first affinity molecule is cross-linked to the antigenic polysaccharide using a cross-linking reagent selected from any in the group consisting of: CDAP (1-cyano-4-dimethylaminopyridinium tetrafluoroborate); EDC (1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride); sodium cyanoborohydride; cyanogen bromide; and ammonium bicarbonate/iodoacetic acid.

4. The immunogenic composition of claim 1 , wherein the pair(s) of the affinity molecules is/are each independently selected from the group consisting of: biotin/biotin-binding protein, antibody/antigen, enzyme/substrate, receptor/ligand, metal/metal-binding protein, carbohydrate/carbohydrate binding protein, lipid/lipid-binding protein, and His tag/His tag-binding substance.

5. The immunogenic composition of claim 1 , wherein the first affinity molecule is biotin or a derivative or mimic molecule thereof.

6. The immunogenic composition of claim 1 , wherein the complementary second affinity molecule is a biotin-binding protein, or an avidin-like protein or a derivative or functional portion thereof.

7. The immunogenic composition of claim 6 , wherein the avidin-like protein is selected from the group consisting of: rhizavidin, avidin, streptavidin, and a homologue or derivative thereof.

8. The immunogenic composition of claim 1 , wherein the antigenic polysaccharide is a branched chain polysaccharide or a straight chain polysaccharide.

9. The immunogenic composition of claim 1 , comprising two to ten different peptide or polypeptide antigens, wherein the peptide or polypeptide antigens are selected from the group consisting of: different peptides or polypeptides; different variants of the same peptide or polypeptide; and different domains or portions of the same peptide or polypeptide.

10. The immunogenic composition of claim 1 , further comprising a flexible linker peptide attached to the peptide or polypeptide antigens, wherein the flexible linker peptide attaches the peptide or polypeptide antigens to the complementary second affinity molecule.

11. The immunogenic composition of claim 1 , wherein at least one of the peptide or polypeptide antigen is from a pathogenic organism, or a cancer or tumor.

12. The immunogenic composition of claim 1 , wherein at least one of the peptide or polypeptide antigens is selected from the group consisting of: tuberculosis antigens; Staphylococcus aureus antigens; Acinetobacter antigens; enteric Gram-negative bacterial antigens; nonenteric Gram-negative bacterial antigens; Gram-positive bacterial antigens; toxoids, toxins or toxin portions; fungal antigens; viral antigens; cancer or tumor antigens; and combinations thereof.

13. The immunogenic composition of claim 1 , wherein the antigenic polysaccharide is selected from the group consisting of: polysaccharides, oligosaccharides, or lipopolysaccharides from Gram-positive bacteria; polysaccharides, oligosaccharides, or lipopolysaccharides from Gram-negative bacteria; other bacterial capsular or cell wall polysaccharides; fungal polysaccharides; viral polysaccharides; and polysaccharides derived from cancer or tumor cells.

14. The immunogenic composition of claim 1 , further comprising at least one co-stimulation factor associated with the antigenic polysaccharide or at least one of the peptide or polypeptide antigens.

15. The immunogenic composition of claim 14 , wherein the co-stimulation factor is selected from the group consisting of: a Toll-like receptor ligand/agonist, a NOD ligand/agonist, and an activator/agonist of an inflammasome.

16. The immunogenic composition of claim 1 , further comprising at least one adjuvant.

17. A method for inducing an immune response in a subject to at least one antigen, comprising administering to the subject a composition of claim 1 .

18. The method of claim 17 , wherein the immune response is an antibody or B cell response.

19. The method of claim 17 , wherein the immune response is a CD4+ T cell response, including Th1, Th2, or Th17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response.

20. The method of claim 17 , wherein the immune response is:
an antibody or B cell response; and
a T cell response.

21. The method of claim 17 , wherein the immune response is to at least one antigenic polysaccharide or at least one peptide or polypeptide antigen.

22. The method of claim 17 , wherein the immune response is an antibody or B cell response to at least one antigenic polysaccharide and a CD4+ T cell response, including Th 1, Th2, or Th 17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one peptide or polypeptide antigen.

23. The method of claim 17 , wherein the immune response is an antibody or B cell response to at least one antigenic polysaccharide, and an antibody or B cell response and a CD4+ T cell response, including Th1, Th2, or Th 17 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one peptide or polypeptide antigen.

24. The immunogenic composition of claim 12 , wherein the enteric Gram-negative bacterial antigens are selected from the group of: E. coli antigens, Salmonella antigens, Enterobacter antigens, Klebsiella antigens, Citrobacter antigens, Serratia antigens, Clostridia antigens, Shigella antigens, Campylobacter antigens, Vibrio cholera antigens, and combinations thereof.

25. The immunogenic composition of claim 12 , wherein the nonenteric Gram-negative bacterial antigens are selected from the group of: Pertussis antigens, Meningococcal antigens, Haemophilus antigens, Pseudomonas antigens, and combinations thereof.

26. The immunogenic composition of claim 12 , wherein the Gram-positive bacterial antigens are pneumococcal antigens or anthrax antigens.

27. The immunogenic composition of claim 12 , wherein the viral antigens are HIV antigens, or seasonal or epidemic influenza antigens.

28. The immunogenic composition of claim 13 , wherein the antigenic polysaccharide is selected from the group consisting of: Salmonella typhi Vi capsular polysaccharides; Salmon

Assignees

• Malley Richard
• Lu Yingjie
• Zhang Fan
• Childrens Medical Ct Corp

Inventors

• Malley Richard
• Lu Yingjie
• Zhang Fan

Classifications

• 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

• C07K14/31 Primary

  from Staphylococcus (G) · CPC title

• C07K14/195

  from bacteria · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K2039/6093

  Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine · CPC title