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US 10,245,318 B2Granted
Flagellin-containing protein nanoparticles as a vaccine platform
AssigneeAlpha-O Peptides AG
InventorsPeter Burkhard, Senthil Kumar Raman, Sara Maria Paulillo, Matteo Piazza, Caroline Kulangara, Christian Mittelholzer
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Abstract
The present invention relates to self-assembling protein nanoparticles constructed from suitable oligomerization domains and further incorporating the TLR5 binding protein flagellin as an adjuvant molecule. Furthermore, the invention relates to the use of such nanoparticles for vaccination.
Claims13
A self-assembling protein nanoparticle consisting of aggregates of a multitude of building blocks of formula (Ia) or (Ib)
- X-ND1-L1-ND2-FLA (Ia)
- or
- FLA-ND1-L1-ND2-X (Ib),
- consisting of a continuous chain comprising a protein oligomerization domain ND1, a linker L1, a protein oligomerization domain ND2, FLA, and a further substituent X, wherein
- ND1 is a protein that forms oligomers (ND1)m of m subunits ND1,
- ND2 is a protein that forms oligomers (ND2)n of n subunits ND2,
- m and n each is a figure between 2 and 10, with the proviso that m is not equal to n and not a multiple of n, and n is not a multiple of m,
- L1 is a bond or a short flexible linker,
- FLA is flagellin, or a derivative of flagellin lacking parts of the flagellin amino acid sequence but at least containing the TLR5 binding domain D1, and wherein the lacking parts are (a) replaced by a flexible linker segment of 1 to 20 amino acids joining two ends of the flagellin amino acid sequence or (b) are replaced by a fully folded protein antigen;
- X is absent or a peptide or protein sequence comprising 1 to 1000 amino acids,
- optionally co-assembled with a multitude of building blocks of the formula (II)
- Y-ND3-L2-ND4-Z (II),
- consisting of a continuous chain comprising a protein oligomerization domain ND3, a linker L2, a protein oligomerization domain ND4, and further substituents Y and Z, wherein
- ND3 is a protein that forms oligomers (ND3)y of y subunits ND3,
- ND4 is a protein that forms oligomers (ND4)z of z subunits ND4,
- y and z each is a figure between 2 and 10, with the proviso that y is not equal to z and not a multiple of z, and z is not a multiple of y, and wherein
- either ND3 is identical to ND1, or ND4 is identical to ND2 or both ND3 and ND4 are identical to ND1 and ND2, respectively,
- L2 is a bond or a short flexible linker that may be different from L1 or identical to L1, and
- Y and Z are, independently of each other, absent or a peptide or protein sequence comprising 1 to 1000 amino acids.
16 more elements
A monomeric building block of formula (Ia) or (Ib)
- X-ND1-L1-ND2-FLA (Ia)
- or
- FLA-ND1-L1-ND2-X (Ib),
- consisting of a continuous chain comprising a protein oligomerization domain ND1, a linker L1, a protein oligomerization domain ND2, FLA, and a further substituent X, wherein
- ND1 is a protein that forms oligomers (ND1)m of m subunits ND1,
- ND2 is a protein that forms oligomers (ND2)n of n subunits ND2,
- m and n each is a figure between 2 and 10, with the proviso that m is not equal to n and not a multiple of n, and n is not a multiple of m,
- L1 is a bond or a short flexible linker,
- FLA is flagellin, or a derivative of flagellin lacking parts of the flagellin amino acid sequence but at least containing the TLR5 binding domain D1, and wherein the lacking parts are (a) replaced by a flexible linker segment of 1 to 20 amino acids joining two ends of the flagellin amino acid sequence or (b) are replaced by a fully folded protein antigen;
- and
- X is absent or a peptide or protein sequence comprising 1 to 1000 amino acids.
8 more elements
Dependencies are inferred from the claim text.