Pneumococcal vaccine containing pneumococcal surface protein A

Patent metadata

Field	Value
Publication number	US-9938326-B2
Application number	US-201314429547-A
Country	US
Kind code	B2
Filing date	Mar 22, 2013
Priority date	Sep 19, 2012
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

A pneumococcal vaccine comprising a fusion protein at least comprising a full-length family 1 pneumococcal surface protein A (PspA) or a fragment thereof, and a full-length family 2 PspA or a fragment thereof, in particular any one of the following fusion proteins (1) to (3):
(1) a fusion protein at least comprising a family 1, clade 2 PspA and a family 2, clade 3 PspA, (2) a fusion protein at least comprising a family 1, clade 2 PspA and a family 2, clade 4 PspA, and (3) a fusion protein at least comprising a family 1, clade 2 PspA and a family 2, clade 5 PspA,

is useful as a pneumococcal vaccine comprising a single protein antigen that has broadly cross-reactive immunogenicity and can induce immune response against a wide range of pneumococcal clinical isolates.

First claim

The invention claimed is:

1. A pneumococcal vaccine for parenteral administration comprising a fusion protein comprising a full-length family 1, clade 2 pneumococcal surface protein A (PspA) or a fragment thereof, and a full-length family 2 PspA or a fragment thereof,
wherein the full-length family 1, clade 2 PspA or a fragment thereof and the full-length family 2 PspA or a fragment thereof each comprises the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, the fragment consists of 108 amino acid residues or more, and the fusion protein possesses the ability to induce protective immunity against pneumococcal infections in a living body,
the fusion protein being any one of the following (1) to (3):

(1) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 3 PspA or a fragment thereof,
(2) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 4 PspA or a fragment thereof, and
(3) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 5 PspA or a fragment thereof.

2. The pneumococcal vaccine according to claim 1 , wherein the fusion protein is any one of the following (4) to (6):
(4) a fusion protein consisting of a fragment of family 1, clade 2 PspA, and fragment of family 2, clade 3 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto,
(5) a fusion protein consisting of a fragment of family 1, clade 2 PspA, and a fragment of family 2, clade 4 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, and
(6) a fusion protein consisting of a fragment of family 1, clade 2 PspA, and a fragment of family 2, clade 5 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto.

3. The pneumococcal vaccine according to claim 1 , wherein the family 1, clade 2 PspA is from a pneumococcal strain selected from the group consisting of D39, WU2, E134, EF10197, EF6796, BG9163 and DBL5.

4. The pneumococcal vaccine according to claim 1 , wherein the family 2, clade 3 PspA is from a pneumococcal strain TIGR4, BG8090 or AC122, the family 2, clade 4 PspA is from a pneumococcal strain EF5668, BG7561, BG7817 or BG11703, and the family 2, clade 5 PspA is from a pneumococcal strain ATCC6303 or KK910.

5. The pneumococcal vaccine according to claim 1 , wherein the fusion protein consists of an amino acid sequence at least 90% identical to SEQ ID NO: 1, 3 or 5.

6. A pneumococcal vaccine for parenteral administration comprising any one of the following (i) to (iii):
(i) a combination of only a fragment of family 1, clade 2 PspA and a fragment of family 2, clade 3 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto,
(ii) a combination of only a fragment of family 1, clade 2 PspA and a fragment of family 2, clade 4 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, and
(iii) a combination of only a fragment of family 1, clade 2 PspA and a fragment of family 2, clade 5 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto.

7. The pneumococcal vaccine according to claim 1 , wherein the fusion protein is any one of the following (4) to (6):
(4) a fusion protein composed of a fragment consisting of the whole of α-helical and proline-rich regions of a D39 PspA, and a fragment consisting of the whole of α-helical and proline-rich regions of an EF5668 PspA,
(5) a fusion protein composed of a fragment consisting of the whole of α-helical and proline-rich regions of a D39 PspA, and a fragment consisting of the whole of α-helical and proline-rich regions of an ATCC6303 PspA, and
(6) a fusion protein composed of a fragment consisting of the whole of α-helical and proline-rich regions of a WU2 PspA, and a fragment consisting of the whole of α-helical and proline-rich regions of a TIGR4 PspA.

8. The pneumococcal vaccine according to claim 7 , wherein the fusion protein is that described in the above (6).

9. The pneumococcal vaccine according to claim 5 , wherein the fusion protein consists of an amino acid sequence at least 90% identical to SEQ ID NO: 5.

10. A method for prevention or treatment of pneumococcal disease, comprising parenterally administering, to an animal, an effective amount of a fusion protein comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2 PspA or a fragment thereof,
wherein the full-length family 1, clade 2 PspA or a fragment thereof and the full-length family 2 PspA or a fragment thereof each comprises the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, the fragment consists of 108 amino acid residues or more, and the fusion protein possesses the ability to induce protective immunity against pneumococcal infections in a living body,
the fusion protein being any one of the following (1) to (3):

(1) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 3 PspA or a fragment thereof,
(2) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 4 PspA or a fragment thereof, and
(3) a fusion protein at least comprising a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2, clade 5 PspA or a fragment thereof.

11. A method for prevention or treatment of pneumococcal disease, comprising parenterally administering, to an animal, effective amounts of at least the following components: a full-length family 1, clade 2 PspA or a fragment thereof, and a full-length family 2 PspA selected from the group consisting of clade 3, 4 and 5 PspAs, or a fragment thereof, wherein the full-length family 1, clade 2 PspA or a fragment thereof, and the full-length family 2 PspA selected from the group consisting of clade 3, 4 and 5 PspAs, or a fragment thereof each comprises the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, the fragment consists of 108 amino acid residues or more, and the components possess the ability to induce protective immunity against pneumococcal infections in a living body.

12. The pneumococcal vaccine according to claim 1 , further comprising an adjuvant.

13. The pneumococcal vaccine according to claim 1 , further comprising a vaccine component against a pathogen other than pneumococci.

14. The method according to claim 10 , wherein the fusion protein is any one of the following (4) to (6):
(4) a fusion protein consisting of a fragment of family 1, clade 2 PspA, and a fragment of family 2, clade 3 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto,
(5) a fusion protein consisting of a fragment of family 1, clade 2 PspA, and h a fragment of family 2, clade 4 PspA, wherein the fragment consists of the whole of a proline-rich region and the whole or part of an α-helical region adjacent thereto, and
(6) a fusion protein consisting of a fragment of family 1, clade 2

Assignees

• Univ Osaka

Inventors

• Akeda Yukihiro
• Piao Zhenyu
• Oishi Kazunori

Classifications

• A61P43/00

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

• A61P31/04

  Antibacterial agents · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07K14/3156 Primary

  from Streptococcus pneumoniae (Pneumococcus) (Streptokinase C07K14/3153) · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title