VLP-based vaccines for targeting
The present invention is directed to virus-like particles (VLPs) which are engineered to present epitopes from Staphylococcus aureus (SA), preferably autoinducing peptides (AIPs) which regulate quorum-sensing dependent virulence in this pathogen, or epitopes from SA toxins and leukocidins. These VLPs may be used to provide immunogenic compositions and efficacious vaccines. In a mouse model of SA dermonecrosis, vaccination with AIP-containing VLPs or SA toxin-containing VLPs induces protective immunity to limit the pathogenesis of SA infection and promote bacterial clearance.
1. A composition comprising: (a) a virus-like particle comprising a single chain dimer of PP7 or MS2 coat protein; and (b) at least one antigen or antigenic determinant according the sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:7, or SEQ ID NO:8 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the A-B loop, N-terminus or carboxy terminus of said coat protein.
2. The composition according to claim 1 wherein said virus-like particle comprises a single chain dimer of PP7.
3. The composition according to claim 1 wherein said virus-like particle comprises a single chain dimer of PP7 and said antigen or antigenic determinant is according to the sequence of SEQ ID NO:1 or SEQ ID NO:2.
4. The composition according to claim 1 wherein said virus-like particle comprises a single chain dimer of PP7 and said antigen or antigenic determinant is according to the sequence of SEQ ID NO:1.
5. The composition according to claim 1 wherein said virus-like particle comprises a single chain dimer of PP7 and said antigen or antigenic determinant is according to the sequence of SEQ ID NO:2.
6. The composition according to claim 1 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the A-B loop.
7. The composition according to claim 2 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the A-B loop.
8. The composition according to claim 3 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the A-B loop.
9. The composition according to claim 1 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the N-terminus.
10. The composition according to claim 2 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the N-terminus.
11. The composition according to claim 3 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the N-terminus.
12. The composition according to claim 1 wherein said antigen or antigenic determinant is displayed on said virus-like particle at the carboxy terminus.
13. A population of virus-like particles according to claim 1 .
14. A population of virus-like particles according to claim 3 .
15. A population of virus-like particles according to claim 4 .
16. A population of virus-like particles according to claim 5 .
17. A pharmaceutical composition comprising a population of virus-like particles according to claim 13 in combination with a pharmaceutically acceptable carrier, additive and/or excipient.
18. A pharmaceutical composition comprising a population of virus-like particles according to claim 14 in combination with a pharmaceutically acceptable carrier, additive and/or excipient.
19. A pharmaceutical composition comprising a population of virus-like particles according to claim 15 in combination with a pharmaceutically acceptable carrier, additive and/or excipient.
20. A pharmaceutical composition comprising a population of virus-like particles according to claim 16 in combination with a pharmaceutically acceptable carrier, additive and/or excipient.