Delivery of RNA to trigger multiple immune pathways
RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.
1. A method of raising an immune response in a vertebrate, comprising administering an immunogen-encoding self-replicating RNA to the vertebrate such that the RNA is translated to provide expression of the immunogen, wherein all of the nucleotides in the RNA are standard A, C, G and U ribonucleotides other than a 5′ cap, wherein the RNA comprises genetic elements required for RNA replication and lacks those genetic elements encoding gene products necessary for viral particle assembly; and wherein the RNA is encapsulated in a liposome delivery system substantially free of viral protein.
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 3 , wherein injection is via a needle.
5. 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.
6. The method of claim 1 , wherein the RNA encodes a tumor antigen.