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-10869920-B2
Application number	US-201916596175-A
Country	US
Kind code	B2
Filing date	Oct 8, 2019
Priority date	Jan 10, 2002
Publication date	Dec 22, 2020
Grant date	Dec 22, 2020

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 virus and comprising:
a cleavage site for joining the dengue virus capsid protein and the West Nile virus prM protein, 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; and
a mutation encoding a threonine at a nucleotide corresponding to nucleotide position 4891 and/or a mutation encoding a proline at a nucleotide corresponding to nucleotide position 4995 of SEQ ID NO: 38.

2. The nucleic acid chimera of claim 1 , wherein the dengue virus is dengue type 1 virus, dengue type 2 virus, dengue type 3 virus, or dengue type 4 virus.

3. The nucleic acid of claim 1 , further comprising a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue genome corresponding to the TL2 stem-loop structure.

4. The nucleic acid chimera of claim 3 , 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.

5. The nucleic acid chimera of claim 3 , 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.

6. The nucleic acid chimera of claim 3 , 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.

7. The nucleic acid chimera of claim 3 , wherein the dengue virus is dengue type 4 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 10478-10507.

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

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

10. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of claim 9 to the subject.

11. The method of claim 10 , 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

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C12N15/86

  Viral vectors · 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

• A61P31/12

  Antivirals · CPC title

• C12N2770/24134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title