Immunisation of large mammals with low doses of RNA
RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.
1. A method of eliciting an antibody response and/or a cell-mediated immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of a self-replicating RNA encoding an immunogen, wherein the large mammal is a human, horse, cattle or pig and the RNA is formulated with a non-viral delivery system that comprises liposomes comprising a cationic lipid comprising a tertiary amine, wherein the self-replicating RNA: i) cannot perpetuate itself in infectious form and ii) includes no modified nucleotides other than a 5′ cap.
2. The method of claim 1 , wherein the RNA is administered to skeletal muscle tissue.
3. The method of claim 1 , wherein the RNA is administered by injection.
4. The method of claim 1 , wherein said RNA does not encode virion structural proteins.
5. The method of claim 1 , wherein the RNA is +-stranded.
6. The method of claim 1 , wherein the RNA encodes an immunogen which can elicit an immune response against a bacterium, a virus, a fungus or a parasite.
7. The method of claim 6 , wherein the immunogen can elicit an immune response in vivo against respiratory syncytial virus glycoprotein F.
8. The method of claim 1 , wherein the large mammal is a cow or a human.
9. The method of claim 1 , wherein said RNA induces production of IgG against said immunogen in said mammal.
10. The method of claim 1 , wherein the antibody and/or cell-mediated immune response is a protective immune response.
11. A method of eliciting an antibody response and/or a cell-mediated immune response in a large mammal, comprising administering to the mammal between 0.1 μg and 1.5 μg RNA per kg of the mammal's body weight, wherein the large mammal is a human, horse, cattle or pig and said RNA is a self-replicating RNA that encodes an immunogen, and wherein said RNA is formulated with a non-viral delivery system that comprises liposomes comprising a cationic lipid comprising a tertiary amine, wherein the self-replicating RNA: i) cannot perpetuate itself in infectious form and ii) includes no modified nucleotides other than a 5′ cap.
12. The method of claim 11 , wherein the RNA is administered to skeletal muscle tissue.
13. The method of claim 11 , wherein the RNA is administered by injection.
14. The method of claim 11 , wherein said RNA does not encode virion structural proteins.
15. The method of claim 11 , wherein the RNA is +-stranded.
16. The method of claim 11 , wherein said mammal is a human, cattle, horse, or pig.
17. The method of claim 11 , wherein the RNA encodes an immunogen which can elicit an immune response against a bacterium, a virus, a fungus or a parasite.
18. The method of claim 17 , wherein the immunogen can elicit an immune response in vivo against respiratory syncytial virus glycoprotein F.
19. The method of claim 11 , wherein the large mammal is a cow or a human.
20. The method of claim 11 , wherein said RNA induces production of IgG against said immunogen in said mammal.