Klebsiella pneumoniae capsule polysaccharide vaccines

Patent metadata

Field	Value
Publication number	US-11097000-B2
Application number	US-201716338501-A
Country	US
Kind code	B2
Filing date	Oct 3, 2017
Priority date	Oct 3, 2016
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The disclosure provides various immunogens comprising a repeat unit of saccharide of Klebsiella pneumoniae CPS, which has a formula selected from the group consisting of Formulae (I) to (VI) as described herein. Also provided are vaccines including one or more immunogens selected from Formula (I) to (VI) and methods of eliciting an immune response against a Klebsiella pneumoniae and preventing infection of Klebsiella pneumoniae by using an immunogen of the invention.

First claim

What is claimed is:

1. An immunogen comprising a repeat unit of trisaccharide of Klebsiella pneumoniae K1 capsular polysaccharide (CPS), which has the following Formula (I):
{→4)-[2,3-(S)-pyruvate]- b -D-GlcAp-(1→4)- a -L-O-Ac-Fucp-(1→3)- b -D-Glcp-(1→} m   (I)

wherein m is 1 to 4; and wherein the Formula (I) is linked to a terminal group consisting of thiol (—SH) at reducing end of the repeat unit.

2. The immunogen of claim 1 , wherein m is 2.

3. An immunogen comprising a repeat unit of tetrasaccharide of Klebsiella pneumoniae K2 CPS, which has the following Formula (II):

wherein n is 1 to 4; and wherein the Formula (II) is linked to a terminal group consisting of thiol (—SH) at reducing end of the repeat unit.

4. The immunogen of claim 3 , wherein the K2 CPS contains one repeat unit (n=1).

5. An immunogen comprising a repeat unit of hexasaccharide of Klebsiella pneumoniae K64 CPS, which has the following Formula (III):

wherein n is 1 to 4, and wherein the Formula (III) is linked to a tell final group consisting of thiol (—SH) at reducing end of the repeat unit.

6. The immunogen of claim 5 , wherein n is 1.

7. An immunogen comprising a repeat unit of pentasaccharide of Klebsiella pneumoniae K62 CPS, which has the following Formula (IV):

wherein n is 1 to 4, and wherein the Formula (IV) is linked to a tell final group consisting of thiol (—SH) at reducing end of the repeat unit.

8. The immunogen of claim 7 , wherein n is 2.

9. An immunogen comprising a repeat unit of pentasaccharide of Klebsiella pneumoniae K 24 CPS, which has the following Formula (V):

wherein n is 1 to 4; and wherein the Formula (V) is linked to a terminal group consisting of thiol (—SH) at reducing end of the repeat unit.

10. The immunogen of claim 9 , wherein n is 1.

11. An immunogen comprising a repeat unit of hexasaccharide of Klebsiella pneumoniae K28 CPS, which has the following Formula (VI):

wherein n is 1 to 4; and wherein the Formula (VI) is linked to a terminal group consisting of thiol (—SH) at reducing end of the repeat unit.

12. The immunogen of claim 11 , wherein n is 1.

13. An immunogen comprising a repeat unit of hexasaccharide of Klebsiella pneumoniae KN2 CPS, which has four hexoses and one hexuronic acid and about a molecule weight of about 1027; wherein the KN2 CPS is linked to a terminal group consisting of thiol (—SH) at reducing end of the repeat unit.

14. A vaccine comprising one or more immunogens comprising one or more digested Klebsiella pneumoniae capsular polysaccharides (CPS) selected from Formula (I) to (VI):
{→4)-[2,3-(S)-pyruvate]- b -D-GlcAp-(1→4)- a -L-O-Ac-Fucp-(1→3)- b -D-Glcp-(1→} m   (I)

wherein Formula (I) belongs to capsular type K1 and m is 1 to 4;

wherein Formula (II) belongs to capsular type K2 and n is 1 to 4;

wherein Formula (III) belongs to capsular type K64 and n is 1 to 4;

wherein Formula (IV) belongs to capsular type K62 and n is 1 to

wherein Formula (V) belongs to capsular type K24 and n is 1 to 4; and

wherein Formula (VI) belongs to capsular type K28 and n is 1 to 4;
wherein each of the Formula (I) to (VI) is linked to a terminal group consisting of thiol (—SH) at reducing end of the CPS.

15. The vaccine of claim 14 , wherein the immunogen is conjugated with a carrier.

16. The vaccine of claim 14 , wherein the vaccine is a K1 and K2 CPS-conjugated divalent vaccine comprising immunogens of Formula (I) and Formula (II).

17. The vaccine of claim 14 , wherein the vaccine is a K1 and K2 CPS-conjugated divalent vaccine comprising a mixture of immunogen I-carrier and immunogen II-carrier, wherein the immunogen I having Formula (I) and the immunogen II having Formula (II) are conjugated with a carrier, respectively.

18. The vaccine of claim 14 , wherein the vaccine is a K64 and K62 CPS-conjugated divalent vaccine comprising immunogens of Formula (III) and Formula (IV).

19. The vaccine of claim 14 , wherein the vaccine is a K64 and K62 CPS-conjugated divalent vaccine comprising a mixture of immunogen III-carrier and immunogen IV-carrier, wherein the immunogen III having Formula (III) and the immunogen IV having Formula (IV) are conjugated with a carrier, respectively.

20. The vaccine of claim 15 , 17 or 19 , wherein the carrier is a protein, a peptide, a lipid, a polymer, a dendrimer, a virosome, a virus-like particle (VLP), or combinations of distinct carriers thereof.

21. The vaccine of claim 15 , 17 or 19 , wherein the carrier is a protein carrier.

22. The vaccine of claim 21 , wherein the protein carrier is selected from the group consisting of a bacterial toxoid, a toxin, an exotoxin, and a nontoxic derivative thereof.

23. The vaccine of claim 21 , wherein the protein carrier is CRM197 having an amino acid sequence as shown in SEQ ID NO:3.

24. A method of eliciting an immune response against a Klebsiella pneumoniae , comprising administering an effective amount of the immunogen of any one of claims 1 to 13 or a vaccine of any one of claims 14 to 23 to a subject.

25. A method of preventing infection of Klebsiella pneumoniae , comprising administering an effective amount of the immunogen of any one of claims 1 to 13 or a vaccine of any one of claims 14 to 23 to a subject.

26. The vaccine of claim 21 , wherein the protein carrier is selected from the group consisting of keyhole limpet hemocyanine (KLH), hepatitis B virus core protein, thyroglobulin, albumins, bovine serum albumin (BSA), human serum albumin (HSA), ovalbumin, pneumococcal surface protein A (PspA), pneumococcal adhesin protein (PsaA), purified protein derivative of tuberculin (PPD), transferrin binding proteins, polyamino acids comprising poly(lysine:glutamic acid), tetanus toxoid, tetanus toxin Fragment C, diphtheria toxoid, CRM (a nontoxic diphtheria toxin mutant), cholera toxoid, Staphylococcus aureus exotoxins or toxoids, Escherichia coli heat labile enterotoxin, Pseudomonas aeruginosa exotoxin A, bacterial outer membrane proteins comprising Neisseria meningitidis serotype B outer membrane protein complex (OMPC) and outer membrane class 3 porin (rPorB).

Assignees

• Univ Nat Taiwan
• Academia Sinica

Inventors

• Wang Jin-Town
• Wu Shih-Hsiung
• Wu Chung-Yi

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K39/0266 Primary

  Klebsiella · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• C08B37/006

  Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof · CPC title

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title