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 virus which:
(i) lacks a functional vhs gene;
(ii) lacks a functional gene encoding ICP47; and
(iii) comprises a functional UL43 gene such that dendritic cells are infected with said virus.
2. The method of claim 1 , wherein said virus is a herpes simplex virus 1 or 2.
3. The method of claim 1 , wherein said virus lacks at least one further functional immediate early gene.
4. The method of claim 3 , wherein said immediate early gene is selected from genes encoding ICP0, ICP4, ICP22 and ICP27.
5. The method of claim 3 , wherein said virus lacks both a functional gene encoding ICP27 and a functional gene encoding ICP4.
6. The method of claim 1 , wherein said virus comprises a heterologous gene.
7. The method of claim 1 , wherein said heterologous gene is operably linked to a control sequence permitting expression of said heterologous gene in a dendritic cell.
8. The method of claim 1 , wherein said heterologous gene encodes a polypeptide of therapeutic use.
9. The method of claim 1 , 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; a polypeptide which is present in or on the surface of tumour cells but absent from non-tumour cells; a polypeptide capable of modifying immune responses; and a polypeptide of parasitic, viral or bacterial origin.
10. The method of claim 1 , wherein said virus comprises more than one heterologous gene.
11. The method of claim 1 , wherein said virus comprises a heterologous gene or genes capable of modulating an immune response.
12. The method of claim 11 , wherein said heterologous gene encodes a chemokine, cytokine, or co-stimulatory molecule.
13. The method of claim 1 , wherein said subject is a human subject.
14. 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.
15. The method of claim 1 , wherein the subject is in need of treatment of or protection against a pathogenic infection.
16. The method of claim 1 , wherein the subject is in need of treatment of or protection against cancer.
17. The method of claim 15 , wherein the pathogenic infection is HSV1 or HSV2 infection.
18. The method of claim 17 , wherein the pathogenic infection is HSV1 infection and the virus is an attenuated HSV1.
19. The method of claim 18 , wherein the pathogenic infection is HSV2 infection and the virus is an attenuated HSV2.