Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) virus-like particles comprising heterologous antigens inserted into the envelope protein
The present invention provides a particle comprising a polypeptide and at least one antigen, and a composition comprising thereof.
1. A Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) virus-like particle which is capable of being self-assembled,
wherein said virus-like particle comprises capsid and envelope proteins,
wherein said virus-like particle comprises a Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) envelope protein with at least one antigen inserted therein,
and wherein the spatial distance between the N-terminal residue and the C-terminal residue of the antigen is 30 Å or less.
2. The virus-like particle according to claim 1 , wherein said virus-like particle is a Chikungunya virus (CHIKV) virus-like particle.
3. The virus-like particle according to claim 1 , wherein said virus-like particle comprises capsid and envelope proteins E2 and E1.
4. The virus-like particle according to claim 3 , wherein said at least one antigen is inserted into said envelope protein E2.
5. The virus-like particle according to claim 1 , wherein said at least one antigen is a polypeptide derived from TNF-α, CD20 or CTLA4.
6. The virus-like particle according claim 1 , wherein said virus-like particle is selected from the group consisting of:
i) a Chikungunya virus (CHIKV) virus-like particle, wherein said at least one antigen is a polypeptide derived from TNF-α;
ii) a Chikungunya virus (CHIKV) virus-like particle, wherein said at least one antigen is a polypeptide derived from CD20;
iii) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein said at least one antigen is a polypeptide derived from TNF-α;
iv) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein said at least one antigen is a polypeptide derived from CD20; and
v) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein said at least one antigen is a polypeptide derived from CTLA4.
7. The virus-like particle according to claim 1 , wherein said at least one antigen is fused to said envelope protein to form a fusion protein.
8. The virus-like particle according to claim 7 , wherein in said fusion protein one or two linkers intervene between the N-terminal residue of said at least one antigen and said envelope protein, and/or between the C-terminal residue of said at least one antigen and said envelope protein.
9. The virus-like particle according to claim 4 , wherein said at least one antigen is inserted into E2 of a CHIKV structural protein that comprises the amino acid sequence of SEQ ID NO: 1 or 2, and wherein said at least one antigen is inserted between residues 519 and 520 of SEQ ID NO: 1 or 2, between residues 530 and 531 of SEQ ID NO: 1 or 2, between residues 531 and 532 of SEQ ID NO: 1 or 2 or between residues 532 and 533 of SEQ ID NO: 1 or 2.
10. The virus-like particle according to claim 7 , wherein said fusion protein is a protein consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs. 4, 5, 6, 7 and 8.
11. A composition comprising the virus-like particle according to claim 1 .
12. A vaccine composition comprising the virus-like particle according to claim 1 .
13. The virus-like particle according to claim 1 , wherein said at least one antigen is selected from the group consisting of self antigens and cancer antigens.