# US 10,869,920 B2 · Construction of West Nile virus and dengue virus chimeras for use in a live virus vaccine to prevent disease caused by West Nile virus

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- Number: US 10,869,920 B2
- Document ID: US10869920B2
- Status: Granted
- Kind: B2
- Application number: 16/596,175
- Filed: 2019-10-08
- Published: 2020-01-30
- Granted: 2020-12-22
- Earliest claimed: 2002-01-10
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services; The Government of the United States, as represented by the Secretary of the Army
- Applicants: The United States of America, as represented by the Secretary, Dept. of Health and Human Services; The Government of the United States, as Represented by The Secretary of The Army
- Inventors: Alexander G. Pletnev; Joseph R. Putnak; Robert M. Chanock; Brian R. Murphy; Stephen S. Whitehead; Joseph E. Blaney
- Web page: https://patentgrep.com/patent/US10869920B2

## CPC

- A61K 39/12: Viral antigens
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- C12Q 1/6888: for detection or identification of organisms
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- C12N 2770/24122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2770/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2770/24143: viral genome or elements thereof as genetic vector
- C12N 2770/24162: by genetic engineering
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 3)

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.

### Claim 6 (depends on 3)

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.

### Claim 7 (depends on 3)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 9)

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

### Claim 11 (depends on 10)

The method of claim 10, wherein the subject is a non-human primate, a human, a horse, or a bird.