CA2293692A1 - Methods and reagents for vaccination which generate a cd8 t cell immune response - Google Patents

Methods and reagents for vaccination which generate a cd8 t cell immune response Download PDF

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CA2293692A1
CA2293692A1 CA002293692A CA2293692A CA2293692A1 CA 2293692 A1 CA2293692 A1 CA 2293692A1 CA 002293692 A CA002293692 A CA 002293692A CA 2293692 A CA2293692 A CA 2293692A CA 2293692 A1 CA2293692 A1 CA 2293692A1
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cell
epitopes
recombinant
kit according
source
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CA2293692C (en
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Andrew James Mcmichael
Adrian Vivian Sinton Hill
Sarah Catherine Gilbert
Joerg Schneider
Magdalena Plebanski
Tomas Hanke
Geoffrey Lilley Smith
Tom Blanchard
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Oxxon Therapeutics Ltd
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Abstract

New methods and reagents for vaccination are described which generate a CD8 T cell immune response against malarial and other antigens such as viral and tumour antigens. Novel vaccination regimes are described which employ a priming composition and a boosting composition, the boosting composition comprising a non-replicating or replication-impaired poxvirus vector carrying at least one CD8 T cell epitope which is also present in the priming composition.

Claims (45)

1. A kit for generating a protective CD8+ T cell immune response against at least one target antigen, which kit comprises:
(i) a priming composition comprising a source of one or more CD8+ T
cell epitopes of the target antigen, together with a pharmaceutically acceptable carrier; and (ii) a boosting composition comprising a source of one or more CD8+ T
cell epitopes of the target antigen, including at least one CD8+ T cell epitope which is the same as a CD8+ T cell epitope of the priming composition, wherein the source of CD8+ T cell epitopes is a non-replicating or replication-impaired recombinant poxvirus vector, together with a pharmaceutically acceptable carrier;
with the proviso that if the source of epitopes in (i) is a viral vector, the viral vector in (ii) is derived from a different virus.
2. The kit according to claim 1, wherein the source of CD8+ T
cell epitopes in (i) is a non-viral vector or a non-replicating or replication-impaired viral vector.
3. The kit according to claim 1 or claim 2, wherein the source of CD8+ T cell epitopes in (i) is not a poxvirus vector.
4. The kit according to claim 2 or claim 3, wherein the source of CD8+ T cell epitopes in (i) is DNA or RNA.
5. The kit according to claim 4, wherein the source of epitopes in (i) is a recombinant DNA plasmid.
6. The kit according to claim 4 or claim 5, further comprising GM-CSF as an adjuvant for (i).
7. The kit according to any one of claims 1 to 6, wherein the source of CD8+ T cell epitopes in (i) encodes or comprises the target antigen.
8. The kit according to any one of claims 4 to 6, wherein the source of epitopes in (i) encodes a single CD8+ T cell epitope or a recombinant string of two or more CD8+ T cell epitopes.
9. The kit according to any one of claims 1 to 3, wherein the source of epitopes in (i) is a peptide, polypeptide, protein, polyprotein or particle comprising two or more CD8+ T cell epitopes, present in a recombinant string of CD8+ T cell epitopes or in a target antigen.
10. The kit according to claim 9, wherein the source of CD8+ T
cell epitopes in (i) is a recombinant protein particle such as a Ty virus-like particle (VLP).
11. The kit according to any one of claims 1 to 3, wherein the source of epitopes in (i) is a recombinant adenovirus vector.
12. The kit according to any one of claims 1 to 11, wherein the source of CD8+ T cell epitopes in (ii) is a recombinant vaccinia virus vector.
13. The kit according to claim 12, wherein the recombinant vaccinia virus vector is of the vaccinia virus strain Modified Virus Ankara (MVA), or a strain derived therefrom.
14. The kit according to claim 12, wherein the recombinant vaccinia virus vector is of the strain NYVAC or a strain derived therefrom.
15. The kit according to any one of claims 1 to 11, wherein the source of CD8+ T cell epitopes in (ii) is a recombinant avipox vector such as canary pox or fowl pox or strains derived therefrom such as ALVAC.
16. The kit according to any one of claims 1 to 15, for generating a protective immune response against a pathogen or tumour comprising the target antigen.
17. The kit according to claim 16, for generating a protective immune response against a malaria pathogen such as Plasmodium falciparum.
18. A kit according to claim 17, wherein the CD8+ T cell epitopes in or encoded by (i) include one or more malaria epitopes from the list given in table 1.
19. The kit according to claim 18, wherein the CD8+ T cell epitopes in (i) include all of the epitopes given in table 1.
20. The kit according to claim 16, for generating an immune response against HIV.
21. The kit according to claim 20, wherein the CD8+ T cell epitopes in or encoded by (i) include one or more HIV epitopes from the list given in table 2.
22. The kit according to claim 20, wherein the CD8+ T cell epitopes in or encoded by (i) include all of the epitopes given in table 2.
23. The kit according to any one of claims 1 to 22, wherein the priming and boosting compositions are identical in that both contain the source of epitopes in (i) and the source of epitopes in (ii).
24. The kit according to any one of claims 1 to 23, wherein the priming composition and/or the boosting composition is in particulate form suitable for delivery by means of a gene gun.
25. A method for generating a protective CD8+ T cell immune response against at least one target antigen, which method comprises administering at least one dose of component (i), followed by at least one dose of component (ii) of the kit according to any one of claims 1 to 24.
26. A method for generating a protective CD8+ T cell immune response against a pathogen or tumour, which method comprises administering at least one dose of a recombinant DNA plasmid encoding at least one CD8+ T cell epitope or antigen of the pathogen or cancer, followed by at least one dose of a recombinant non-replicating or replication-impaired pox virus encoding the same epitope or antigen.
27. The method according to claim 25, wherein the recombinant vaccinia virus is a recombinant MVA vector.
28. A method for generating a protective CD8+ T cell immune response against a pathogen or tumour, which method comprises administering at least one dose of a recombinant protein or particle comprising at least one epitope or antigen of the pathogen or cancer, followed by at least one dose of a recombinant MVA vector encoding the same epitope or antigen.
29. The method according to any one of claims 26 to 28, for generating a protective CD8+ T cell immune response against malaria such as P. falciparum malaria.
30. The method according to any one of claims 26 to 28, for generating a protective CD8+ T cell immune response against HIV.
31. The method according to any one of claims 25 to 30, wherein (ii) is delivered intravenously, intraepidermally or intradermally.
32. A medicament for boosting a primed CD8+ T cell response against at least one target antigen, comprising a source of one or more CD8+ T cell epitopes of the target antigen, wherein the source of CD8+ T
cell epitopes is a non-replicating or a replication-impaired recombinant poxvirus vector, and a pharmaceutically acceptable carrier.
33. The medicament according to claim 32, wherein the vector is a vaccinia virus vector such as MVA.
34. The medicament according to claim 32 or 33, for boosting a naturally primed CD8+ T cell response against malaria.
35. A method of boosting a primed CD8+ T cell immune response, which method comprises administering a medicament according to any one of claims 32 to 34.
36. The use of a recombinant non-replicating or replication-impaired pox virus vector in the manufacture of a medicament for boosting a CD8+ T cell immune response.
37. The use of an MVA vector in the manufacture of a medicament for boosting a CD8+ T cell immune response.
38, An epitope string comprising the amino acid sequences listed in table 1.
39, A recombinant Ty-VLP comprising the epitope string according to claim 38, for immunising against malaria.
40. A recombinant DNA plasmid or recombinant non-replicating or replication-impaired pox virus encoding the epitope string according to claim 38, for immunising against malaria.
41. A replication-impaired pox virus encoding the P, falciparum antigen TRAP, for immunising against malaria.
42. A recombinant vaccinia virus according to claim 40 or claim 41, of the MVA strain.
43. An epitope string comprising the amino acid sequences listed in table 2.
44. A recombinant polypeptide comprising a whole or substantially whole protein antigen and a string of two or more CTL
epitopes from malaria.
45. A recombinant polypeptide as claimed in claim 44, wherein the whole or substantially whole protein antigen is TRAP.
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