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-10456461-B2
Application number	US-201816025624-A
Country	US
Kind code	B2
Filing date	Jul 2, 2018
Priority date	Jan 10, 2002
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

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 dengue type 1 virus, dengue type 2 virus, or dengue type 3 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 and wherein a cleavage site is utilized for joining the dengue virus capsid protein and the 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 wherein the cleavage site corresponds to amino acid position 3 of SEQ ID NO: 3.

2. The nucleic acid chimera of claim 1 , wherein the dengue virus is an attenuated virus or a virus adapted for increased growth in Vero cells.

3. The nucleic acid chimera of claim 1 , wherein the dengue virus is dengue type 1 virus and the virus is attenuated by a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 1 genome corresponding to the TL2 stem-loop structure between about nucleotides 10562-10591.

4. The nucleic acid chimera of claim 1 , wherein the dengue virus is dengue type 2 virus and the virus is attenuated by a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 2 genome corresponding to the TL2 stem-loop structure between about nucleotides 10541-10570.

5. The nucleic acid chimera of claim 1 , wherein the dengue virus is dengue type 3 virus and the virus is attenuated by a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 3 genome corresponding to the TL2 stem-loop structure between about nucleotides 10535-10565.

6. A virus chimera comprising one or more than one nucleic acid chimera of claim 1 .

7. An immunogenic composition comprising one or more than one nucleic acid chimera of claim 1 and a pharmaceutically acceptable carrier.

8. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of claim 7 to the subject.

9. The method of claim 8 wherein the subject is a non-human primate, a human, a horse, or a bird.

10. A vaccine composition comprising one or more than one nucleic acid chimera of claim 1 and a pharmaceutically acceptable carrier.

11. A method of immunizing a subject against West Nile virus infection comprising administering an effective amount of the composition of claim 10 to the subject.

12. The method of claim 11 wherein the subject is a non-human primate, a human, a horse, or a bird.

Assignees

• Us Health
• Us Gov Sec Army

Inventors

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

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• C12N2770/24122

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

• C12N2770/24143

  viral genome or elements thereof as genetic vector · CPC title