Ii vaccine adjuvant

Patent metadata

Field	Value
Publication number	US-11179461-B2
Application number	US-201816484336-A
Country	US
Kind code	B2
Filing date	Mar 19, 2018
Priority date	Mar 20, 2017
Publication date	Nov 23, 2021
Grant date	Nov 23, 2021

Abstract

The present invention relates to a vaccine comprising a nucleic acid construct such as a DNA construct especially a nucleic acid construct comprising sequences encoding invariant chain operatively linked to antigenic protein or peptide encoding sequences. The present vaccine stimulates an enhanced immune response.

First claim

The invention claimed is:

1. A nucleic acid construct comprising sequences encoding:
a. at least one invariant chain or variant thereof operatively linked to
b. at least one antigenic protein or peptide or an antigenic fragment thereof;
wherein
the C-terminal end of said invariant chain or variant thereof is operatively linked to the N-terminal end of said antigenic protein or peptide or antigenic fragment thereof;
said invariant chain or variant thereof comprises a protease cleavage site for a protease selected from the group consisting of furin and subtilisin-like proteases, and optionally a trimerization (TRIM) domain located C-terminally of said protease cleavage site, wherein the protease cleavage site is located between the MHC-II interaction peptide (CLIP) region and the C-terminus of the invariant chain.

2. The nucleic acid construct according to claim 1 , wherein the encoded at least one invariant chain shares at least 90% identity to any one of SEQ ID NOs: 1, 3, 4, 6, 7, 9, 11 or 13-50.

3. The nucleic acid construct according to claim 2 , wherein the encoded at least one invariant chain is identical to any one of SEQ ID NOs: 1, 3, 4, 6, 7, 9, 11 or 13-50.

4. The nucleic acid construct according to claim 1 , wherein the encoded variant of invariant chain is a fragment of SEQ ID NO: 3 of at least 40 amino acids and has at least 85% identity to the same fragment of SEQ ID NO: 3.

5. The nucleic acid construct according to claim 1 , wherein the encoded at least one invariant chain comprises a region encoding a transmembrane domain.

6. The nucleic acid construct according to claim 1 , wherein the at least one antigenic protein or peptide or an antigenic fragment thereof is derived from a pathogen selected from the group consisting of viruses, bacteria, protozoa and multicellular parasites.

7. The nucleic acid construct according to claim 1 , wherein at least one antigenic protein or peptide or an antigenic fragment thereof is from a cancer-specific polypeptide.

8. The nucleic acid construct according to claim 1 , wherein the invariant chain and the antigenic protein or peptide or antigenic fragment thereof are linked by a direct link or a link mediated by a spacer region.

9. The nucleic acid according to claim 1 , wherein the nucleic acid is comprised within a delivery vehicle, wherein the delivery vehicle is selected from the group of: RNA based vehicles, DNA based vehicles/vectors, lipid based vehicles, polymer-based vehicles and virally derived DNA or RNA vehicles.

10. The nucleic acid according to claim 9 , wherein the delivery vehicle is an adenovirus.

11. The nucleic acid according to claim 1 wherein the protease cleavage site is a furin cleavage site.

12. The nucleic acid according to claim 11 wherein the furin cleavage site comprises or consists of the sequence RXR/KR (SEQ ID NO: 70) wherein X is any of the 20 naturally occurring amino acids.

13. The nucleic acid according to claim 12 wherein the furin cleavage site comprises SEQ ID NO: 57.

14. A method for inducing an immune response in an animal, comprising administering to the animal composition comprising the nucleic acid according to claim 1 which is operably linked to a promoter for expression of said nucleic acid.

15. The nucleic acid according to claim 13 wherein the furin cleavage site consists of SEQ ID NO: 57.

Assignees

• Univ Copenhagen

Inventors

• Holst Peter Johannes
• Fougeroux Cyrielle Elyette

Classifications

• A61K39/00119

  Melanoma antigens · CPC title

• A61K39/39 Primary

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K14/045

  Cytomegalovirus · CPC title

• C07K14/025

  Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus · CPC title