Shigella multiple antigen presenting immunogenic composition and fusion proteins thereof
AssigneeChildren's Medical Center Corporation
InventorsRichard MALLEY, Fan ZHANG, Yingjie LU
Life of this patent
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Abstract
Technologies for the prevention and/or treatment of Shigella infections.
Claims164
A vaccine comprising an immunogenic complex, wherein the immunogenic complex comprises:
- (a) a biotinylated polysaccharide antigen;
- and
- (b) a fusion protein comprising:
- ii. a biotin-binding moiety;
- and
- iii. at least one polypeptide antigen;
- wherein the biotinylated polysaccharide antigen comprises a 0-specific polysaccharide (OSP) of Shigella, and further wherein the biotinylated polysaccharide antigen is non-covalently associated with the biotin-binding moiety of the fusion protein to form an immunogenic complex.
The vaccine of any one of the preceding claims, wherein the at least one polypeptide antigen of the fusion protein is or comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 4.
The vaccine of any one of the preceding claims, wherein the at least one polypeptide antigen of the fusion protein is or comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 5.
The vaccine of any one of the preceding claims, wherein the at least one polypeptide antigen of the fusion protein is or comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to either SEQ ID NO:
- 8 or SEQ ID NO:
- 9, or a combination of SEQ ID NO:
- 8 and SEQ ID NO:
- 9.
The vaccine of any one of the preceding claims, wherein the biotin-binding moiety is a polypeptide comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 3 or a biotin-binding fragment thereof.
An immunogenic composition (e.g., a vaccine) comprising a plurality of different species of immunogenic complexes, wherein the different species comprise:
- a plurality of biotinylated polysaccharide antigens comprising polysaccharide antigens of one or more Shigella serotypes;
- and
- a plurality of fusion proteins, each fusion protein comprising:
- a biotin-binding moiety;
- and
- a polypeptide antigen,
- wherein each of the plurality of biotinylated polysaccharide antigens is non-covalently associated with the biotin-binding moiety of one or more of the plurality of fusion proteins to form an immunogenic complex.
A vaccine comprising a plurality of different species of immunogenic complexes, wherein the different species comprise:
- a biotinylated polysaccharide antigen of Shigella serotype S. Flexneri 2a non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. Flexneri 3a non-covalently complexed with a fusion protein;
- wherein each fusion protein comprises
- a biotin-binding moiety;
- and
- a first polypeptide antigen comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 4, SEQ ID NO:
- 5, or either SEQ ID NO:
- 8, SEQ ID NO:
- 9, or both SEQ ID NO:
- 8 and SEQ ID NO:9, or an antigenic fragment thereof, and
- wherein each of the biotinylated polysaccharide antigens is non-covalently associated with the biotin-binding moiety of at least one fusion protein to form an immunogenic complex.
A vaccine comprising a plurality of different species of immunogenic complexes, wherein the different species comprise:
- a biotinylated polysaccharide antigen of Shigella serotype S. Flexneri 6 non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. Sonnei non-covalently complexed with a fusion protein;
- wherein each fusion protein comprises
- a biotin-binding moiety;
- and
- a first polypeptide antigen comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 4, SEQ ID NO:
- 5, or either SEQ ID NO:
- 8, SEQ ID NO:
- 9, or both SEQ ID NO:
- 8 and SEQ ID NO:9, or an antigenic fragment thereof, and
- wherein each of the biotinylated polysaccharide antigens is non-covalently associated with the biotin-binding moiety of at least one fusion protein to form an immunogenic complex.
A vaccine comprising a plurality of different species of immunogenic complexes, wherein the different species comprise:
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 2a non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 3a non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 6 non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. sonnei non-covalently complexed with a fusion protein;
- wherein each fusion protein comprises
- a biotin-binding moiety;
- and
- a first polypeptide antigen comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% SEQ ID NO:
- 4, SEQ ID NO:
- 5, or either SEQ ID NO:
- 8, SEQ ID NO:
- 9, or both SEQ ID NO:
- 8 and SEQ ID NO:9, or an antigenic fragment thereof, and
- wherein each of the biotinylated polysaccharide antigens is non-covalently associated with the biotin-binding moiety of at least one fusion protein to form an immunogenic complex.
A vaccine comprising a plurality of different species of immunogenic complexes, wherein the different species comprise:
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 2a non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 3a non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. flexneri 6 non-covalently complexed with a fusion protein;
- a biotinylated polysaccharide antigen of Shigella serotype S. sonnei non-covalently complexed with a fusion protein;
- wherein each fusion protein comprises
- a biotin-binding moiety;
- a first polypeptide antigen comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 4, SEQ ID NO:
- 5, or either SEQ ID NO:
- 8, SEQ ID NO:
- 9, or both SEQ ID NO:
- 8 and SEQ ID NO:
- 9, or an antigenic fragment thereof, and
- a second polypeptide antigen comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 4, SEQ ID NO:
- 5, or either SEQ ID NO:
- 8, SEQ ID NO:
- 9, or both SEQ ID NO:
- 8 and SEQ ID NO:9, or an antigenic fragment thereof, and
- wherein each of the biotinylated polysaccharide antigens is non-covalently associated with the biotin-binding moiety of at least one fusion protein to form an immunogenic complex.
The vaccine of any one of the preceding claims, wherein the biotin-binding moiety is a polypeptide comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO:
- 3.
An immunogenic complex comprising a biotinylated polysaccharide antigen of Shigella non-covalently associated with a fusion protein, wherein the fusion protein comprises a biotin-binding moiety and at least one polypeptide antigen.
A method of making a vaccine, comprising non-covalently complexing a plurality of biotinylated polysaccharide antigens with a plurality of fusion proteins, wherein each fusion protein comprises at least one polypeptide antigen selected SseB, IpaB, SP0785 or SP1500;
- wherein the plurality of biotinylated polysaccharide antigens comprises polysaccharides of one or more Shigella serotypes selected from Typhimurium, Enteritidis, Typhi, and Paratyphi A.
A fusion protein comprising a rhizavidin protein and at least one peptide or polypeptide antigen, wherein the rhizavidin protein comprises amino acids of SEQ ID NO:
- 3, or 85% sequence identity to amino acids of SEQ ID NO:
- 3, and Salmonella peptide or polypeptide comprises a fragment of at least 20 amino acids of the SseB protein, or the Shigella peptide or polypeptide comprises a fragment of at least 20 amino acids of the IpaB protein.
A vaccine composition comprising at least two immunogenic complexes selected from any combination of Shigella-MAPS immunogenic complexes listed in Table 2A, and at least two or more immunogenic complexes selected from any of the Salmonella-MAPS immunogenic complexes listed in any of Tables 3A, 3B or 3C.
A fusion proteincomprising, in any order:
- a. a biotin-binding moiety and
- b.a IpaB polypeptide.
- wherein the fusion protein comprises (i) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 3 (Rhavi) and (ii) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 5 (IpaB).
A fusion protein comprising, in any order:
- a. a biotin-binding moiety and
- b.a SseB polypeptide.
- wherein the fusion protein comprises (i) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 3 (Rhavi) and (ii) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 4 (SseB).
An immunogenic composition comprising at least at least one species of immunogenic complex,
- wherein each species of the immunogenic complex comprises:
- (a) a biotinylated polysaccharide antigen comprising biotin and a 0-specific polysaccharide (OSP) antigen from a Shigella spp serogroup, and
- (b) a fusion protein comprising:
- (i) a biotin-binding moiety;
- and
- (ii) at least one polypeptide antigen comprising a IpaB polypeptide,
- wherein the fusion protein comprises (i) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 3 (Rhavi) and (ii) an amino acid sequence that has at least 80% identical to SEQ ID NO:
- 5(IpaB), or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:
- 4 (SseB), and
- wherein in each species of the immunogenic complexes, the biotinylated OSP antigen is non-covalently associated with the biotin-binding moiety of the fusion protein.
A heterologous nucleic acid sequence encoding a fusion proteincomprising, in any order:
- a. a biotin-binding moiety and
- b.a IpaB polypeptide,
- wherein the fusion protein comprises (i) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 3 (Rhavi) and (ii) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 5(IpaB).
A heterologous nucleic acid sequence encoding a fusion proteincomprising, in any order:
- a. a biotin-binding moiety and
- b.a SseB polypeptide,
- wherein the fusion protein comprises (i) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 3 (Rhavi) and (ii) an amino acid sequence that is at least 80% identical to SEQ ID NO:
- 4 (SseB).
Dependencies are inferred from the claim text.