Nucleoside-modified mRNA-lipid nanoparticle lineage vaccine for hepatitis C virus

Patent metadata

Field	Value
Publication number	US-12226471-B2
Application number	US-202318310066-A
Country	US
Kind code	B2
Filing date	May 1, 2023
Priority date	Apr 27, 2017
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

The present invention relates to compositions and methods for inducing an adaptive immune response against Hepatitis C virus (HCV) in a subject. In some embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof. For example, in some embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof.

First claim

What is claimed is:

1. A lineage vaccine for inducing an immune response against Hepatitis C virus (HCV) in a subject comprising a combination of isolated nucleoside-modified RNA molecules, wherein the combination of isolated nucleoside-modified RNA molecules encodes a combination of sequential lineage antigens for inducing an immune response against Hepatitis C virus (HCV) in a subject, wherein the combination of isolated nucleoside-modified RNA molecules comprises at least one isolated nucleoside-modified RNA molecule encoding each of the HCV antigens as set forth in SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18.

2. The lineage vaccine of claim 1 , wherein each isolated nucleoside-modified RNA molecule comprises at least one modified nucleoside selected from the group consisting of pseudouridine and 1-methyl-pseudouridine.

3. The lineage vaccine of claim 1 , wherein each isolated nucleoside-modified RNA molecule is a purified nucleoside-modified RNA.

4. The lineage vaccine of claim 1 , wherein the combination of nucleoside-modified RNA molecules comprises RNA sequences encoded by DNA sequences comprising: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9.

5. The lineage vaccine of claim 1 , wherein the composition further comprises an adjuvant or wherein at least one nucleoside-modified RNA molecule further encodes at least one adjuvant.

6. The lineage vaccine of claim 1 , comprising a combination of lipid nanoparticles (LNPs) wherein the combination of LNPs encapsulates isolated nucleoside-modified RNA molecules encoding each of the HCV antigens as set forth in SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18.

7. The lineage vaccine of claim 6 , wherein each isolated nucleoside-modified RNA molecule is encapsulated within a different LNP.

8. A method of inducing an adaptive immune response against Hepatitis C virus (HCV) in a subject comprising administering to the subject an effective amount of a lineage vaccine of claim 1 .

9. The method of claim 8 , wherein each isolated nucleoside-modified RNA molecule comprises at least one modified nucleoside selected from the group consisting of pseudouridine and 1-methyl-pseudouridine.

10. The method of claim 8 , wherein each isolated nucleoside-modified RNA molecule is a purified nucleoside-modified RNA.

11. The method of claim 8 , wherein the combination of nucleoside-modified RNA molecules comprises RNA sequences encoded by DNA sequences comprising: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9.

12. The method of claim 8 , wherein the method further comprises administering to the subject an effective amount of an adjuvant.

13. The method of claim 8 , wherein at least one nucleoside-modified RNA molecule further encodes at least one adjuvant.

14. The method of claim 8 , wherein the lineage vaccine comprises a combination of lipid nanoparticles (LNPs) wherein the combination of LNPs encapsulates isolated nucleoside-modified RNA molecules encoding each of the HCV antigens as set forth in SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18.

15. The method of claim 14 , wherein each nucleoside-modified RNA molecule is encapsulated within a different LNP.

16. The method of claim 8 , wherein the lineage vaccine is administered by a delivery route selected from the group consisting of intravenous, intradermal, subcutaneous, inhalation, intranasal, and intramuscular.

17. The method of claim 8 , wherein the method comprises a single administration of the lineage vaccine.

18. The method of claim 8 , wherein the method comprises multiple administrations of the lineage vaccine.

19. The method of claim 8 , wherein the method treats or prevents an infection, disease, or disorder associated with HCV in the subject.

Assignees

• Univ Pennsylvania
• Univ Johns Hopkins
• Univ Vanderbilt

Inventors

• Weissman Drew
• Shaw George M
• Bailey Justin R
• Ray Stuart C
• Crowe Jr James
• Flyak Andrew

Classifications

• A61K39/29

  Hepatitis virus · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K2039/55555

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

• A61K2039/53

  DNA (RNA) vaccination · CPC title