# US 12,370,254 B2 · Dendritic cell-targeting universal vaccine for influenza infection

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- Number: US 12,370,254 B2
- Document ID: US12370254B2
- Status: Granted
- Kind: B2
- Application number: 17/768,624
- Filed: 2020-10-21
- Published: 2024-06-06
- Granted: 2025-07-29
- Earliest claimed: 2019-10-21
- Assignees: University of Manitoba
- Applicants: University of Manitoba
- Inventors: Xiao-Jian Yao
- Web page: https://patentgrep.com/patent/US12370254B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/295: Polyvalent viral antigens (vaccinia virus or variola virus A61K39/285); Mixtures of viral and bacterial antigens
- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61P 31/16: for influenza or rhinoviruses
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- A61K 2039/5258: {Virus-like particles}
- C07K 2319/00: Fusion polypeptide
- C12N 2740/16023: Virus like particles [VLP]
- C12N 2740/16043: viral genome or elements thereof as genetic vector
- C12N 2760/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/14134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/20243: viral genome or elements thereof as genetic vector
- 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)

## Abstract

We have recently developed a novel DC-targeting vaccine platform using Ebola glycoprotein (EboGP) DC-targeting domain-based fusion protein technology. Here, we will use this technology to generate universal vaccines against Influenza A by fusing a DC-targeting/activation domain (EboGPAM), derived from EboGP to I) a tetrameric conserved extracellular domain of M2 (M2e) of Influenza A strains from human, birds, and swine; 2) the conserved stalk regions (HAcs) of HA and an M2 polypeptide from H5N1 strain; and 3) the HA head regions polypeptides (HAH5-1-3) derived from H5N1, H1 N1 and H3N2 strains.

## Claims

### Claim 1

A fusion protein comprising an influenza virus surface protein peptide inserted in the mucin-like domain of a Filoviridae Virus glycoprotein wherein the influenza virus surface protein is selected from the group consisting of hemagglutinin and matrix-2 and the influenza virus surface protein peptide comprises 6 or more consecutive amino acids of the influenza virus surface protein.

### Claim 2 (depends on 1)

The fusion protein according to claim 1 wherein the peptide comprises 6 or more consecutive amino acids of a conserved region of hemagglutinin or matrix-2 or 6 or more consecutive amino acids of globular head domain of hemagglutinin.

### Claim 3 (depends on 1)

The fusion protein according to claim 1 wherein the fusion peptide comprises more than one influenza virus surface protein peptide and each respective influenza virus surface protein peptide is separated from an adjacent influenza virus surface protein peptide by a spacer.

### Claim 4 (depends on 1)

The fusion protein according to claim 1 wherein the mucin-like domain is a tolerated deletion of the mucin-like domain.

### Claim 5 (depends on 1)

The fusion peptide according to claim 1 wherein the fusion peptide comprises the amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3.

### Claim 6

A method of targeting an influenza virus surface protein peptide to a dendritic cell comprising:
providing virus-like particles comprising as glycoprotein a Filoviridae Virus glycoprotein fusion protein comprising an influenza virus surface protein peptide inserted in the mucin-like domain of the Filoviridae Virus glycoprotein wherein the influenza virus surface protein is selected from the group consisting of hemagglutinin and matrix-2 and the influenza virus surface protein peptide comprises 6 or more consecutive amino acids of the influenza virus surface protein; and
immunizing an individual with the virus-like particles.

### Claim 7 (depends on 6)

The method according to claim 6 wherein the Filoviridae virus is Ebola virus or Marburg virus.

### Claim 8 (depends on 6)

The method according to claim 6 wherein the influenza virus surface protein peptide comprises 6 or more consecutive amino acids of a conserved region of hemagglutinin or matrix-2 or 6 or more consecutive amino acids of globular head domain of hemagglutinin.

### Claim 9 (depends on 6)

The method according to claim 6 wherein the fusion peptide comprises more than one influenza virus surface protein peptide and each respective influenza virus surface protein peptide is separated from an adjacent influenza virus surface protein peptide by a spacer.

### Claim 10 (depends on 6)

The method according to claim 6 wherein the mucin-like domain is a tolerated deletion of the mucin-like domain.

### Claim 11 (depends on 6)

The method according to claim 6 wherein the fusion peptide comprises the amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO: 2 or SEQ ID NO: 3.

### Claim 12

A method of eliciting an immune response against an influenza surface protein peptide in an individual comprising:
providing virus-like particles comprising as glycoprotein a Filoviridae Virus glycoprotein fusion protein comprising an influenza virus surface protein peptide inserted in the mucin-like domain of the Filoviridae Virus glycoprotein wherein the influenza virus surface protein is selected from the group consisting of hemagglutinin and matrix-2 and the influenza virus surface protein peptide comprises 6 or more consecutive amino acids of the influenza virus surface protein; and
immunizing an individual in need of immunization against influenza virus with an effective amount of the virus-like particles.

### Claim 13 (depends on 12)

The method according to claim 12 wherein the Filoviridae virus is Ebola virus or Marburg virus.

### Claim 14 (depends on 12)

The method according to claim 12 wherein the peptide comprises 6 or more consecutive amino acids of a conserved region of hemagglutinin or matrix-2 or 6 or more consecutive amino acids of globular head domain of hemagglutinin.

### Claim 15 (depends on 12)

The method according to claim 12 wherein the fusion peptide comprises more than one influenza virus surface protein peptide and each respective influenza virus surface protein peptide is separated from an adjacent influenza virus surface protein peptide by a spacer.

### Claim 16 (depends on 12)

The method according to claim 12 wherein the mucin-like domain is a tolerated deletion of the mucin-like domain.

### Claim 17 (depends on 12)

The method according to claim 12 wherein the fusion peptide comprises the amino acid sequence as set forth in SEQ ID No:1, SEQ ID No: 2 or SEQ ID No. 3.