Combined vaccine against mycobacterium tuberculosis

Patent metadata

Field	Value
Publication number	US-12090198-B2
Application number	US-201816616258-A
Country	US
Kind code	B2
Filing date	May 18, 2018
Priority date	May 22, 2017
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

The present embodiments provide for a Mycobacterium tuberculosis ( M. tuberculosis ) Multiple Antigen Presenting System (MAPS) immunogenic composition comprising an immunogenic polysaccharide which induces an immune response, where at least one M. tuberculosis peptide or polypeptide antigen is associated to the immunogenic polysaccharide by complementary affinity molecules. In some embodiments, the immunogenic polysaccharide can be an antigenic capsular polysaccharide of a Mycobacterium tuberculosis , Type 5 (CP5) or Type 8 (CP8), or a combination of Type 5 or Type 8 capsular polysaccharide from Staphylococcus aureus , or alternatively, a different immunogenic capsular or noncapsular polysaccharide, and where the protein or peptide M. tuberculosis antigens are indirectly linked via an affinity binding pair. The present M. tuberculosis -MAPS immunogenic compositions can elicit both humoral and cellular immune responses to the immunogenic polysaccharide and one or multiple M. tuberculosis antigens at the same time.

First claim

The invention claimed is:

1. An immunogenic composition comprising an immunogenic complex, the immunogenic complex comprising:
at least two biotinylated polysaccharide antigens,
a lipidated biotin-binding protein; and
a first fusion protein comprising:
(i) a biotin-binding moiety and
(ii) at least a MPT51 peptide antigen
wherein at least the one of the biotinylated polysaccharide is non-covalently associated with the lipidated biotin-binding protein and at least one of the biotinylated polysaccharides is non-covalently associated with the biotin-binding moiety of the fusion protein.

2. The immunogenic composition of claim 1 , wherein the immunogenic complex can further comprise a second fusion protein, the second fusion protein comprising:
(i) a biotin-binding moiety;
(ii) at least a first Mycobacterium tuberculosis (Mtb) peptide antigen; and
(iii) at least a second Mycobacterium tuberculosis (Mtb) peptide antigen
wherein the at least first Mtb peptide antigen is selected from any of the group comprising: ESAT6, CFP10, MPT64, MPT83, TB9.8, TB10.4, PPE41, and PE25 and wherein the at least second Mtb peptide antigen is selected from any of the group comprising: ESAT6, CFP10, MPT64, MPT83, TB9.8, TB10.4, PPE41, and PE25.

3. The immunogenic composition of claim 2 , wherein the second fusion protein comprising the at least two Mtb peptide antigens comprises any of:
(i) an MPT51 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT64, MPT83, TB9.8, TB10.4, PPE41 and PE25;
(ii) an ESAT6 antigen, fused to one or more Mtb peptide antigens selected from any of: CFP10, MPT51, M64, MPT83, TB9.8, TB10.4, PPE41 and PE25;
(iii) a CFP10 antigen, fused to one or more Mtb peptide antigens selected from any of: MPT51, MPT64, MPT83, TB9.8, TB10.4, PPE41 and PE25;
(iv) a MPT64 antigen, fused to one or more Mtb peptide antigens selected from any of: MPT51, ESAT6, CFP10, MPT64, MPT83, TB9.8, TB10.4, PPE41 and PE25
(v) an MPT84 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT51, MPT64, MPT83, TB9.8, TB10.4, PPE41 and PE25
(vi) a TB9.8 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT51, MPT64, MPT83, TB10.4, PPE41 and PE25;
(vii) a TB10.4 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT51, MPT64, MPT83, TB9.8, PPE41 and PE25;
(viii) a PEE41 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT51, MPT64, MPT83, TB9.8, TB10.4 and PE25; or
(ix) a PE25 antigen, fused to one or more Mtb peptide antigens selected from any of: ESAT6, CFP10, MPT51, MPT64, MPT83, TB9.8, TB10.4 and PEE41.

4. The immunogenic composition of claim 3 , wherein the second fusion protein comprises any one of the following:
(i) an ESAT6 antigen fused to at least one fragment of CFP10 antigen,
(ii) an ESAT6 antigen fused to two fragments of CFP10 antigens,
(iii) a TB9.8 antigen fused to a TB10.4 antigen,
(iv) a PPE41 antigen fused to PE25 antigen;
(v) MPT51 antigen, and an ESAT6 antigen, a CFP10 antigen, a MPT64 antigen, a MPT83, a TB9.8 antigen and a TB10.4 antigen
(vi) an ESAT6 antigen fused to at least one fragment of CFP10 antigen and a MPT64 antigen; and
(vii) a TB9.8 antigen fused to a TB10.4 antigen and a MPT86 antigen.

5. The immunogenic composition of claim 2 , wherein the second fusion protein comprises at least three Mtb peptide antigens selected from:
(i) ESAT6, CFP10 and MPT64,
(ii) a ESAT6 antigen, at least two CFP10 antigens and at least a MPT64 antigen,
(iii) TB9.8, TB10.4 and MPT83.

6. The immunogenic composition of claim 2 , wherein the second fusion protein comprising at least two Mtb peptide antigens can comprise at least one linker peptide between each antigen.

7. The immunogenic composition of claim 2 , wherein the first or second Mtb peptide antigen is selected from any of:
(i) a MPT51 antigen comprises at least SEQ ID NO: 3 or a polypeptide with at least 85% sequence identity to SEQ ID NO: 3;
(ii) a MPT51 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 3 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 3;
(iii) an ESAT6 antigen that comprises at least SEQ ID NO: 5 or a polypeptide with at least 85% sequence identity to SEQ ID NO: 4
(iv) an ESAT6 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 5 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO:5;
(v) a CFP10 antigen that comprises at least SEQ ID NO: 6 or SEQ ID NO: 7 or at least or a polypeptide with at least 85% sequence identity to SEQ ID NO: 6 or SEQ ID NO: 7;
(vi) a CFP10 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO:6 or SEQ ID NO: 7 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 6 or SEQ ID NO: 7;
(vii) a MPT64 antigen that comprises at least SEQ ID NO: 9 or a polypeptide with at least 85% sequence identity to SEQ ID NO: 9;
(viii) a MPT64 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO:9 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 9;
(ix) a MPT83 antigen that comprises at least SEQ ID NO: 11 or a polypeptide with at least 85% sequence identity to SEQ ID NO: 11;
(x) a MPT83 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 11 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 11;
(xi) a TB9.8 antigen that comprises at least SEQ ID NO: 13 or a polypeptide with at least 85% sequence identity to SEQ ID NO: 13;
(xii) a TB9.8 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 13 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 13;
(xiii) a TB10.4 antigen that comprises at least SEQ ID NO: 14 or a polypeptide with at least 85% sequence identity to a portion of SEQ ID NO: 14;
(xiv) a TB10.4 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 14 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 14;
(xv) a PPE41 antigen that comprises at least SEQ ID NO: 15 or a polypeptide with at least 85% sequence identity a portion of SEQ ID NO: 15;
(xvi) a PPE41 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 15 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 15;
(xvii) a PE25 antigen that comprises at least SEQ ID NO: 16 or a polypeptide with at least 85% sequence identity a portion of SEQ ID NO: 15; or
(xviii) a PE25 antigen that comprises a fragment of at least 30 amino acids of SEQ ID NO: 16 or a polypeptide of at least 30 amino acids that has at least 85% sequence identity to a portion of SEQ ID NO: 16.

8. The immunogenic composition of claim 1 , wherein the biotin-binding protein of the fusion protein is selected from: an avidin-like protein or lipidated biotin-binding protein, or a lipidated avidin-like protein.

9. The immunogenic composition of claim 8 , wherein the avidin-like protein or lipidated avidin-like protein is selected from the group consisting of: rhizavidin, avidin, streptavidin, or a homologue or derivative thereof.

10. The immunogenic composition of claim 8 , wherein the rhizavidin protein is selected from any of:
(i) a rhizavidin protein that comprises amino acids of SEQ ID NO: 1, or a peptide or protein having 85% sequence identity t

Assignees

• Childrens Medical Ct Corp

Inventors

• Zhang Fan
• Malley Richard
• Lu Yingjie

Classifications

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• C07K14/465

  from birds · CPC title

• C07K14/35 Primary

  from Mycobacteriaceae (F) · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/625

  binding through the biotin-streptavidin system or similar · CPC title