Delivery of RNA to trigger multiple immune pathways

Patent metadata

Field	Value
Publication number	US-10532067-B2
Application number	US-201715725858-A
Country	US
Kind code	B2
Filing date	Oct 5, 2017
Priority date	Jul 6, 2010
Publication date	Jan 14, 2020
Grant date	Jan 14, 2020

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Geall Andrew
• Ramsauer Katrin
• Otten Gillis
• Mandl Christian Walter

Classifications

• C12N2760/18522

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K31/7088 Primary

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• C12N2760/18534

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title