Herpes viruses for immune modulation
View Patent ↗An attenuated herpes virus which lacks a functional vhs gene or a functional equivalent thereof, but which has a functional UL43 gene or functional equivalent thereof, stimulates an immune response when dendritic cells are infected with the virus.
1. A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes simplex virus (HSV) which:
lacks a functional vhs gene;
lacks a functional gene encoding ICP47; and
lacks a functional ICP34.5 gene.
2. The method of claim 1 , wherein said HSV is HSV 1 or HSV 2.
3. The method of claim 1 , wherein said virus comprises a heterologous gene.
4. The method of claim 3 , wherein said heterologous gene is operably linked to a control sequence permitting expression of said heterologous gene in a dendritic cell.
5. The method of claim 3 , wherein said heterologous gene encodes a polypeptide of therapeutic use.
6. The method of claim 3 , wherein said heterologous gene encodes a polypeptide selected from: a polypeptide, the level of expression of which is increased in or on the surface of tumour cells as compared to non-tumour cells; and a polypeptide which is present in or on the surface of tumour cells but absent from non-tumour cells.
7. The method of claim 3 , wherein said virus comprises more than one heterologous gene.
8. The method of claim 5 , wherein said heterologous gene encodes a polypeptide selected from the group consisting of: a polypeptide capable of modulating an immune response; and a polypeptide of parasitic, viral or bacterial origin.
9. The method of claim 8 , wherein said heterologous gene capable of modulating an immune response encodes a chemokine, cytokine or co-stimulatory molecule.
10. The method of claim 1 , wherein said subject is a human subject.
11. The method of claim 1 , wherein the virus is administered by injection, by infusion, by an intra- or trans-dermal route or by biolistic means.
12. The method of claim 8 , wherein the subject is in need of treatment of or protection against a pathogenic infection.
13. The method of claim 6 , wherein the subject is in need of treatment of or protection against cancer.
14. The method of claim 2 , wherein said subject is in need of treatment of, or protection against, HSV1 or HSV2 infection.
15. The method of claim 8 , wherein said heterologous gene is an HSV gene that is not operably linked to the viral control sequences with which it is naturally associated.
16. A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes simplex virus (HSV) which:
(i) lacks a functional vhs gene;
(ii) lacks a functional gene encoding ICP47;
(iii) lacks a functional ICP34.5 gene; and
(iv) comprises a functional UL43 gene.
17. The method of claim 16 , wherein said HSV is HSV1 or HSV2.
18. The method of claim 17 , wherein said subject is in need of treatment of or protection against HSV1 or HSV2 infection.
19. The method of claim 16 , wherein said virus comprises a heterologous gene.
20. The method of claim 19 , wherein said heterologous gene is operably linked to a control sequence permitting expression of said heterologous gene in a dendritic cell.
21. The method of claim 19 , wherein said heterologous gene encodes a polypeptide selected from the group consisting of: a polypeptide, the level of expression of which is increased in or on the surface of tumour cells as compared to non-tumour cells; and a polypeptide which is present in or on the surface of tumour cells but absent from non-tumour cells.
22. The method of claim 21 , wherein the subject is in need of treatment of or protection against cancer.
23. The method of claim 19 , wherein said heterologous gene encodes a polypeptide selected from the group consisting of: a polypeptide capable of modifying immune responses; and a polypeptide of parasitic, viral or bacterial origin.
24. The method of claim 23 , wherein the subject is in need of treatment of or protection against a pathogenic infection.
25. The method of claim 23 , wherein said heterologous gene is an HSV gene that is not operably linked to the viral control sequences with which it is naturally associated.
26. The method of claim 16 , wherein said subject is a human subject.