Construction of West Nile virus and dengue virus chimeras for use in a live virus vaccine to prevent disease caused by West Nile virus

Patent metadata

Field	Value
Publication number	US-10058602-B2
Application number	US-201414305572-A
Country	US
Kind code	B2
Filing date	Jun 16, 2014
Priority date	Jan 10, 2002
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The present invention relates to attenuated, immunogenic West Nile virus chimeras built on a dengue virus backbone for the production of immunogenic, live, attenuated West Nile virus vaccines.

First claim

What is claimed is:

1. A nucleic acid chimera comprising a first nucleotide sequence encoding two structural proteins from a West Nile virus, wherein the structural proteins are premembrane/membrane (prM) and envelope (E), and a second nucleotide sequence encoding capsid (C) and nonstructural proteins from a wild-type strain of dengue virus, wherein the dengue virus is attenuated by a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue genome corresponding to the TL2 stem-loop structure.

2. The nucleic acid chimera of claim 1 , wherein the dengue virus is selected from the group consisting of dengue type 1 virus, dengue type 2 virus, dengue type 3 virus, and dengue type 4 virus.

3. The nucleic acid chimera of claim 1 , wherein the dengue virus is adapted for increased growth in Vero cells.

4. The nucleic acid chimera of claim 3 , wherein the dengue virus is dengue type 4 virus and the deletion of about 30 nucleotides from the 3′ untranslated region corresponds to nucleotides 10478-10507.

5. The nucleic acid chimera of claim 3 , wherein the dengue virus is dengue type 1 virus and the deletion of about 30 nucleotides from the 3′ untranslated region corresponds to nucleotides 10562-10591.

6. The nucleic acid chimera of claim 3 , wherein the dengue virus is dengue type 2 virus and the deletion of about 30nucleotides from the 3′ untranslated region corresponds to nucleotides 10541-10570.

7. The nucleic acid chimera of claim 3 , wherein the dengue virus is dengue type 3 virus and the deletion of about 30nucleotides from the 3′ untranslated region corresponds to nucleotides 10535-10565.

8. The nucleic acid chimera of claim 1 , wherein the dengue virus is dengue type 4 virus, wherein a cleavage site is utilized for joining a dengue virus capsid protein and a West Nile virus prM protein, and wherein the West Nile virus prM protein contains aspartic acid (Asp) at a position 3 amino acids downstream of the cleavage site and contains threonine (Thr) at a position 6 amino acids downstream of the cleavage site.

9. A virus chimera comprising at least one of the nucleic acid chimera of claim 1 .

10. An immunogenic composition comprising the nucleic acid chimera of claim 1 and a pharmaceutically acceptable carrier.

11. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of claim 10 to the subject.

12. The method of claim 11 , wherein the subject is selected from the group consisting of a non-human primate, a human, a horse, and a bird.

13. A vaccine composition comprising the nucleic acid chimera of claim 1 and a pharmaceutically acceptable carrier.

14. A method for immunizing a subject against West Nile Virus infection comprising administering an effective amount of the composition of claim 13 to the subject.

15. The method of claim 14 , wherein the subject is selected from the group consisting of a non-human primate, a human, a horse, and a bird.

Assignees

• Us Health
• Us Army
• The Us Secretary Department Of Health & Human Services
• The Walter Reed Army Institute Of Res

Inventors

• Pletnev Alexander G
• Putnak Joseph R
• Chanock Robert M
• Murphy Brian R
• Whitehead Stephen S
• Blaney Joseph E

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title

• C12N2770/24122

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