Modified virus-like particles of bacteriophage ap205
AssigneeSaiba GmbH
InventorsKaspars TARS, Ilva LIEKNINA, Darja CERNOVA
Life of this patent
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Abstract
The present invention relates to a modified virus-like particle of RNA bacteriophage AP205 (AP205 VLP) comprising AP205 coat protein dimers to which antigenic polypeptides are fused at the N-terminus and/or at the C-terminus. The modified AP205 VLPs can be used as a platform, in particular for vaccine development, in generating immune responses against a variety of antigens.
Claims15
A modified virus-like particle of RNA bacteriophage AP205 (AP205 VLP) comprising one or more fusion proteins, wherein said fusion protein comprises, preferably consists of,
- (i) an AP205 coat protein dimer, wherein said AP205 coat protein dimer comprises a first AP205 polypeptide and a second AP205 polypeptide, wherein said first AP205 polypeptide is fused at its C-terminus either directly or via an amino acid spacer to the N-terminus of said second AP205 polypeptide, and wherein said first and said second AP205 polypeptide independently comprises
- (a) an amino acid sequence of a coat protein of RNA bacteriophage AP205, or
- (b) a mutated amino acid sequence, wherein said mutated amino acid sequence (b) and said amino acid sequence of said coat protein of RNA bacteriophage AP205 (a), have a sequence identity of at least 90%, preferably of at least 95%, further preferably of at least 98% and again more preferably of at least 99%;
- and
- (ii) an antigenic polypeptide, wherein said antigenic polypeptide is fused to the N-terminus and/or the C-terminus of said AP205 coat protein dimer either directly or via an amino acid linker.
The modified AP205 VLP of any one of the preceding claims, wherein said amino acid linker is selected from the group consisting of:
- (a.) a polyglycine linker (Gly)n of a length of n=2-10, preferably a length of n=2-5;
- and
- (b.) a glycine-serine linker (GS-linker) comprising at least one glycine and at least one serine, wherein preferably said GS linker has an amino acid sequence of (GS)r(GsSw)t(GS)u with r=0 or 1, s=1-5, w=0 or 1;
- t=1-3 and u=0 or 1;
- and wherein preferably said glycine-serine linker has a length of at most 15 amino acids;
- (c.) an amino acid linker comprising at least one Gly, at least one Ser, and at least one amino acid selected from Thr, Ala, Lys, Asp and Glu, wherein said amino acid sequence has a length of at most 15 amino acids.
The modified AP205 VLP of any one of the preceding claims, wherein said AP205 coat protein dimer comprises, preferably consists of, the amino sequence of SEQ ID NO:
- 7 or an amino acid sequence having a sequence identity of at least 90%, preferably of at least 95%, further preferably of at least 98% and again more preferably of at least 99% with said SEQ ID NO:
- 7.
The modified AP205 VLP of any one of the preceding claims, wherein an antigenic polypeptide is fused directly or via an amino acid linker to the N-terminus of said AP205 coat protein dimer and an antigenic polypeptide is fused directly or via an amino acid linker to the C-terminus of said AP205 coat protein dimer.
The modified AP205 VLP of any one of the preceding claims, wherein said modified AP205 VLP consists of said fusion proteins.
The modified AP205 VLP of any one of the preceding claims, wherein said antigenic polypeptide is a polypeptide derived from the group consisting of:
- (a) allergens;
- (b) viruses;
- (c) bacteria;
- (d) parasites;
- (e) tumors;
- (f) self-molecules;
- (g) hormones;
- (h) growth factors;
- (i) cytokines;
- and (j) chemokines.
The composition of any one of the preceding claims, wherein said antigenic polypeptide is selected from
- (a) IL-17, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, SEQ ID NO:36;
- (b) IL-5, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:37 to SEQ ID NO:42;
- (c) IL-4, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:43 to SEQ ID NO:45;
- (d) IL-13, and wherein preferably said antigenic polypeptide comprises, or preferably consists of SEQ ID NO:49;
- (e) IL-1α, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:50 to SEQ ID NO:53;
- (f) IL-33, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:54 to SEQ ID NO:58;
- (g) IL-25, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:59 to SEQ ID NO:62;
- (h) IL-1β, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:63 to SEQ ID NO:67;
- (i) IL-12/23;
- (j) TNF-α;
- (k) IL-31, wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:68 to SEQ ID NO:71;
- (l) thymic stromal lymphopoietin (TLSP), wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:72 to SEQ ID NO:75;
- (m) the dog allergen Can f1 or Can f2;
- (n) myostatin, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, SEQ ID NO:87;
- (o) an antigenic polypeptide derived from Plasmodium falciparum or Plasmodium Vivax, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, SEQ ID NO:88;
- (p) CspZ protein from Borrelia burgdorferi, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, SEQ ID NO:89 or SEQ ID NO:90;
- (q) an antigenic polypeptide derived from RSV;
- (r) Dengue viral antigenic polypeptide, wherein preferably said Dengue viral antigenic polypeptide comprises, or preferably consists of, SEQ ID NO:91 or SEQ ID NO:92;
- (s) an antigenic polypeptide derived from a receptor binding domain (RBD) or a receptor binding motif (RBM) of a coronavirus (CoV), preferably of SARS-CoV-2, and wherein preferably said antigenic polypeptide comprises, or preferably consists of, any one the SEQ ID NO:94 to SEQ ID NO:97;
- (t) an antigenic polypeptide derived from African Swine Fever;
- (u) calcitonin gene-related peptide (CGRP);
- (v) Amylin;
- and
- (w) GnRH.
The modified AP205 VLP of any one of the preceding claims, wherein said fusion protein is selected from the group consisting of SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:21, SEQ ID NO:24, SEQ ID NO:101, SEQ ID NO:106 and SEQ ID NO:110.
A modified virus-like particle of RNA bacteriophage AP205 (AP205 VLP) comprising one or more AP205 coat protein dimer, wherein said AP205 coat protein dimer comprises a first AP205 polypeptide and a second AP205 polypeptide, wherein said first AP205 polypeptide is fused at its C-terminus either directly or via an amino acid spacer to the N-terminus of said second AP205 polypeptide, and wherein said first and said second AP205 polypeptide independently comprises
- (a) an amino acid sequence of a coat protein of RNA bacteriophage AP205, or
- (b) a mutated amino acid sequence, wherein said mutated amino acid sequence (b) and said amino acid sequence of said coat protein of RNA bacteriophage AP205 (a), have a sequence identity of at least 90%, preferably of at least 95%, further preferably of at least 98% and again more preferably of at least 99%.
Dependencies are inferred from the claim text.