Virus like particle composition
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, wherein said virus-like particle contains at least one antigen inserted into an E2 envelope protein to form a fusion protein,
wherein the at least one antigen is inserted within a CHIKV E2 envelope protein within a region that corresponds in position to residues 509-512, residues 519-520, or residues 529-533 of SEQ ID NO: 1 or 2; or wherein the at least one antigen is inserted within a VEEV E2 envelope protein within a region that corresponds in position to residues 515-520, or residues 536-539 of SEQ ID NO: 3.
2. The virus-like particle according to claim 1 , wherein the at least one antigen is a self-antigen or a cancer antigen.
3. The virus-like particle according to claim 1 , wherein the at least one antigen is a polypeptide derived from TNF-α, CD20 or CTLA4.
4. The virus-like particle according to claim 1 , wherein said virus-like particle is selected from the group consisting of:
i) a Chikungunya virus (CHIKV) virus-like particle, wherein the at least one antigen is TNF-α;
ii) a Chikungunya virus (CHIKV) virus-like particle, wherein the at least one antigen is CD20;
iii) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein the at least one antigen is TNF-α;
iv) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein the at least one antigen is CD20; and
v) a Venezuelan equine encephalitis virus (VEEV) virus-like particle, wherein the at least one antigen is CTLA4.
5. The virus-like particle according to claim 1 , wherein the at least one antigen is directly fused to the envelope protein.
6. The virus-like particle according to claim 1 , wherein one or two linkers intervene between the N-terminal residue of the at least one antigen and the envelope protein, and/or between the C-terminal residue of the at least one antigen and the envelope protein.
7. The virus-like particle according to claim 1 , wherein the at least one antigen is inserted into a CHIKV E2 envelope protein that comprises the amino acid sequence of SEQ ID NO: 1 or 2, and wherein the 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.
8. The virus-like particle according to claim 1 , wherein said fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 5, 6, 7 and 8.
9. The virus-like particle according to claim 1 , wherein said fusion protein comprises an amino acid sequence having 90% or more sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 5, 6, 7 and 8.
10. A composition comprising the virus-like particle according to claim 1 .
11. A pharmaceutical composition comprising:
(a) the virus-like particle according to claim 1 ; and
(b) a pharmaceutically acceptable carrier.
12. A vaccine composition comprising the virus-like particle according to claim 1 .
13. The virus-like particle according to claim 1 , wherein the at least one antigen is inserted into a VEEV E2 envelope protein that comprises the amino acid sequence of SEQ ID NO: 3, and wherein the at least one antigen is inserted between residues 515 and 516 of SEQ ID NO: 3, between residues 516 and 517 of SEQ ID NO: 3, between residues 517 and 518 of SEQ ID NO: 3, between residues 518 and 519 of SEQ ID NO: 3, between residues 519 and 520 of SEQ ID NO: 3, between residues 536 and 537 of SEQ ID NO: 3, between residues 537 and 538 of SEQ ID NO: 3, or between residues 538 and 539 of SEQ ID NO: 3.
14. The virus-like particle according to claim 1 , wherein the at least one antigen is inserted into a CHIKV E2 envelope protein that comprises the amino acid sequence of SEQ ID NO: 1 or 2, and wherein the at least one antigen is inserted between residues 519 and 520 of SEQ ID NO: 1 or 2, between residues 529 and 530 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, between residues 532 and 533 of SEQ ID NO: 1 or 2, between residues 509 and 510 of SEQ ID NO: 1 or 2, between residues 510 and 511 of SEQ ID NO: 1 or 2, or between residues 511 and 512 of SEQ ID NO: 1 or 2.