Synthetic viruses and uses thereof
View Patent ↗The present invention relates to compositions and methods for producing an immune response or reaction, as well as to vaccines, kits, processes, cells and uses thereof. This invention more particularly relates to compositions and methods of using a synthetic viral particle to produce, modify or regulate an immune response in a subject. In a more preferred embodiment, the invention is based, generally, on compositions using synthetic viral particles as an adjuvant and/or vehicle to raise an immune response against selected antigen(s) or epitopes, in particular a cellular and/or a humoral immune response.
1. An immunogenic composition comprising a non-infectious synthetic retroviral particle comprising: a core comprising at least one self-assembling retroviral Gag protein of a particular retrovirus that is fused in-frame with a heterologous peptide antigen; and a lipid bilayer envelope; wherein the non-infectious synthetic retroviral particle is devoid of any retroviral genome; wherein the non-infectious synthetic retroviral particle is devoid of wild-type infectious envelope protein of the particular retrovirus; and wherein the immunogenic composition comprises at least about 10^2 to about 10^9 of the synthetic retroviral particles.
2. The immunogenic composition of claim 1 , wherein the Gag protein fused with the heterologous peptide antigen is contained within the synthetic retroviral particle.
3. The immunogenic composition of claim 1 , wherein the Gag protein fused with the heterologous peptide antigen is not exposed on the retroviral particle surface.
4. The immunogenic composition of claim 1 , wherein the heterologous peptide antigen comprises a synthetic peptide.
5. The immunogenic composition of claim 4 , wherein the synthetic peptide is between 3 and 60 amino acids in length.
6. The immunogenic composition of claim 1 , wherein the self-assembling retroviral Gag is fused in-frame at its C-terminal end with the heterologous peptide antigen.
7. An immunogenic composition comprising a non-infectious synthetic retroviral particle comprising: a core comprising a self-assembling retroviral Gag protein of a particular retrovirus that is fused in-frame with a first heterologous peptide antigen; and a lipid bilayer envelope in which a second selected peptide antigen that is heterologous to any retrovirus is embedded and exposed at the surface of the particle; wherein the non-infectious synthetic retroviral particle is devoid of any retroviral genome; wherein the non-infectious synthetic retroviral particle is devoid of wild-type infectious envelope protein of the particular retrovirus: and wherein the immunogenic composition comprises at least about 10^2 to about 10^9 of the synthetic retroviral particles.
8. The immunogenic composition of claim 7 , wherein the Gag protein fused with the first heterologous peptide antigen is contained within the synthetic retroviral particle.
9. The immunogenic composition of claim 7 , wherein the Gag protein fused with the first heterologous peptide antigen is not exposed on the retroviral particle surface.
10. The immunogenic composition of claim 7 , wherein the second selected peptide antigen is a glycopeptide antigen.
11. The immunogenic composition of claim 7 , wherein one or both of the first heterologous peptide antigen and the second selected peptide antigen or comprise a synthetic peptide.
12. The immunogenic composition of claim 11 , wherein the synthetic peptide is between 3 and 60 amino acids in length.
13. The immunogenic composition of claim 7 , wherein the self-assembling retroviral Gag protein is fused in-frame at its C-terminal end with the first heterologous peptide antigen.
14. The immunogenic composition of claim 1 , further comprising a pharmaceutically acceptable vehicle.
15. The immunogenic composition of claim 7 , further comprising a pharmaceutically acceptable vehicle.
16. A method of stimulating an immune response in a subject, said method comprising administering the immunogenic composition of claim 14 to said subject.
17. The method of claim 16 , wherein the immune response in the subject includes a cytotoxic T-lymphocyte (CTL) response.
18. A method of stimulating an immune response in a subject, said method comprising administering the immunogenic composition of claim 15 to said subject.
19. The method of claim 18 , wherein the immune response in the subject includes a humoral response and a cytotoxic T-lymphocyte (CTL) response.
20. The immunogenic composition of claim 14 , further comprising an adjuvant.
21. The immunogenic composition of claim 15 , further comprising an adjuvant.