Zika viral antigen constructs

Patent metadata

Field	Value
Publication number	US-11780885-B2
Application number	US-201716461503-A
Country	US
Kind code	B2
Filing date	Nov 15, 2017
Priority date	Nov 17, 2016
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

Compounds useful as components of immunogenic compositions for the induction of an immunogenic response in a subject against viral infection, methods for their use in treatment, and processes for their manufacture are provided herein. The compounds comprise a nucleic acid construct comprising a sequence which encodes a Zika virus antigen.

First claim

We claim:

1. A self-replicating RNA molecule encoding (i) a polypeptide comprising a Zika virus prME antigen which comprises amino acids 21 through 692 of SEQ ID NO: 2 or a polypeptide which comprises a region that is at least 90% identical to the amino sequence of SEQ ID NO:2 or an immunogenic fragment thereof comprising a contiguous amino acid sequence of at least 8 amino acids which is identical to a contiguous amino acids sequence of the full-length Zika virus prME antigen and (ii) a Japanese Encephalitis Virus (JEV) signal sequence comprising SEQ ID NO:5 or a sequence with at least 90% sequence identity to SEQ ID NO:5.

2. The self-replicating RNA molecule of claim 1 which comprises a nucleic acid sequence selected from the group consisting of:
a. a nucleic acid sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:19 or SEQ ID NO:24;
b. a nucleic acid sequence comprising the RNA sequence of SEQ ID NO:39 or SEQ ID NO:40; and
c. a nucleic acid sequence comprising the RNA sequence of SEQ ID NO:36 or SEQ ID NO:37.

3. A DNA molecule encoding the self-replicating RNA molecule of claim 1 .

4. A composition comprising an immunologically effective amount of the self-replicating RNA molecule of claim 1 .

5. The composition of claim 4 , wherein the composition comprises a non-viral delivery material, selected from a submicron cationic oil-in-water emulsion; a liposome; or a biodegradable polymeric microparticle delivery system.

6. The composition of claim 5 , wherein the submicron cationic oil-in-water emulsion comprises an oil core, a cationic lipid, and a surfactant.

7. The composition of claim 4 wherein the composition further comprises one or more nucleic acid sequences which encode one or more additional antigens and/or the composition further comprises one or more additional antigens.

8. The composition of claim 4 wherein the composition comprises one or more adjuvants.

9. A method of inducing an immune response against a Zika virus infection in a subject in need thereof, which comprises administering to said subject an immunologically effective amount of a self-replicating RNA molecule of claim 1 .

10. A method of inducing an immune response against a Zika virus infection in a subject in need thereof, which comprises administering to said subject an immunologically effective amount of the composition of claim 5 .

11. The method of claim 10 wherein the subject is human.

12. A process for producing an RNA-based vaccine comprising a step of transcribing a DNA that encodes the self-replicating RNA molecule of claim 1 to produce said self-replicating RNA molecule.

13. The process of claim 12 , wherein said transcription is in vitro.

14. The process of claim 12 , further comprising a step of formulating the self-replicating RNA with a non-viral delivery system.

15. The process of claim 14 , wherein the delivery system is selected from the group consisting of: a submicron cationic oil-in-water emulsion; a liposome; and a biodegradable polymeric microparticle delivery system.

16. The process of claim 12 , further comprising a step of combining the self-replicating RNA with an additional composition comprising an adjuvant.

17. The process of claim 16 , wherein said adjuvant comprises an immunostimulant.

18. The composition of claim 4 , which induces sterilizing immunity in Rhesus macaques.

19. The composition of claim 4 , which produces a 4-fold change in neutralizing titers when inoculated into Rhesus macaques.

Assignees

• Glaxosmithkline Biologicals Sa
• Us Health

Inventors

• Dowd Kimberly
• Graham Barney S
• Ko Sung-Youl
• Kong Wing-Pui
• Mascola John
• Pierson Theodore
• Sharma Mayuri
• Yu Dong

Classifications

• C07K14/005 Primary

  from viruses · CPC title

• A61K39/12 Primary

  Viral antigens · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• C12N2770/24122

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