# US 10,478,490 B2 · Herpes simplex virus combined subunit vaccines and methods of use thereof

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- Number: US 10,478,490 B2
- Document ID: US10478490B2
- Status: Granted
- Kind: B2
- Application number: 12/270,772
- Filed: 2008-11-13
- Published: 2011-10-20
- Granted: 2019-11-19
- Earliest claimed: 2006-12-28
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: Harvey Friedman; Sita Awasthi; John Lubinski
- Inventors: Harvey Friedman; Sita Awasthi; John Lubinski
- Web page: https://patentgrep.com/patent/US10478490B2

## CPC

- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61K 39/12: Viral antigens
- A61P 31/22: for herpes 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)
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/541: {Mucosal route}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- C07K 2319/21: containing a His-tag
- C12N 2710/16622: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/16634: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2710/16662: by genetic engineering
- 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

This invention provides vaccines comprising two or more recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of impeding immune evasion by HSV thereby vaccinating a subject against HSV and treating, suppressing, inhibiting, and/or reducing an incidence of an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.

## Claims

### Claim 1

An immunogenic composition comprising two or three recombinant Herpes Simplex Virus type 2 (HSV-2) glycoproteins and an adjuvant, said two or three glycoproteins consisting of:
(a) a recombinant HSV-2 glycoprotein E (gE) or immunogenic fragment thereof, wherein said gE fragment comprises amino acids 24-224 or 24-409 of gE as set forth in SEQ ID NO: 6; and
(b) a recombinant HSV-2 glycoprotein D (gD) or immunogenic fragment thereof, a recombinant HSV-2 glycoprotein C (gC) or fragment thereof, or a combination thereof,
wherein said gC fragment comprises a C3b-binding domain of gC,
wherein said immunogenic composition does not comprise HSV-2 glycoprotein B (gB); and
wherein said immunogenic composition has a synergistically greater anti-HSV immune evasion function-blocking as compared with anti-HSV immune evasion function-blocking of one of the components of said immunogenic composition.

### Claim 2 (depends on 1)

The immunogenic composition of claim 1, wherein said adjuvant comprises a CpG-containing nucleotide molecule, an aluminum salt adjuvant, or a combination thereof.

### Claim 3 (depends on 1)

The immunogenic composition of claim 1, wherein said recombinant HSV gD protein or immunogenic fragment thereof is present in an amount of 2-150 micrograms per dose.

### Claim 4 (depends on 1)

The immunogenic composition of claim 1, wherein said recombinant HSV gE protein or immunogenic fragment thereof is present in an amount of 20-100 micrograms per dose.

### Claim 5 (depends on 1)

The immunogenic composition of claim 1, wherein said gE fragment consists of amino acids 24-224 or 24-409 of SEQ ID NO: 6.

### Claim 6 (depends on 1)

The immunogenic composition of claim 1, wherein said recombinant HSV gC protein or fragment thereof is present in an amount of 0.5-100 micrograms per dose.

### Claim 7 (depends on 1)

The immunogenic composition of claim 1, wherein said gC fragment comprises amino acids 27-426 of SEQ ID NO: 4 or a homolog thereof from another HSV-2 strain.

### Claim 8 (depends on 7)

The immunogenic composition of claim 7, wherein said gC fragment consists of amino acids 27-426 of SEQ ID NO: 4 or a homolog thereof from another HSV-2 strain.

### Claim 9 (depends on 1)

A method of inducing an anti-Herpes Simplex Virus (HSV) immune response in a subject, the method comprising the step of administering to said subject the immunogenic composition of claim 1.

### Claim 10 (depends on 9)

The method of claim 9, wherein said immunogenic composition is administered intramuscularly.

### Claim 11 (depends on 9)

The method of claim 9, wherein said immunogenic composition is administered before exposure to HSV.

### Claim 12 (depends on 9)

The method of claim 9, further comprising the step of administering to said subject a booster immunization.

### Claim 13 (depends on 9)

The method of claim 9, wherein said immunogenic composition is administered after exposure to HSV.

### Claim 14 (depends on 9)

The method of claim 9, wherein said subject is HIV-infected.

### Claim 15 (depends on 1)

A method of treating, inhibiting, or reducing an incidence of an Herpes Simplex Virus (HSV) infection in a subject comprising the step of administering to said subject the immunogenic composition of claim 1.

### Claim 16 (depends on 15)

The method of claim 15, wherein said HSV infection is an HSV-1 infection.

### Claim 17 (depends on 15)

The method of claim 15, wherein said HSV infection is an HSV-2 infection.

### Claim 18 (depends on 15)

The method of claim 15, wherein said HSV infection is a genital HSV infection.

### Claim 19 (depends on 15)

The method of claim 15, wherein said HSV infection is an oral HSV infection.

### Claim 20 (depends on 15)

The method of claim 15, wherein said immunogenic composition is administered intramuscularly.

### Claim 21 (depends on 15)

The method of claim 15, wherein said immunogenic composition is administered before exposure to HSV.

### Claim 22 (depends on 15)

The method of claim 15, wherein said HSV infection is a primary HSV infection.

### Claim 23 (depends on 15)

The method of claim 15, wherein said immunogenic composition is administered after exposure to HSV.

### Claim 24 (depends on 15)

The method of claim 15, wherein said HSV infection is a flare, recurrence, or HSV labialis following a primary HSV infection.

### Claim 25 (depends on 15)

The method of claim 15, wherein said HSV infection is a reactivation of a latent HSV infection.

### Claim 26 (depends on 15)

The method of claim 15, wherein said subject is HIV-infected.

### Claim 27

An immunogenic composition comprising two or three recombinant Herpes Simplex Virus type 2 (HSV-2) glycoproteins and an adjuvant, said two or three glycoproteins consisting of:
(a) a recombinant HSV-2 glycoprotein E (gE) or immunogenic fragment thereof, wherein said gE fragment comprises amino acids 24-224 or 24-409 of gE as set forth in SEQ ID NO: 6; and
(b) a recombinant HSV-2 glycoprotein C (gC) or fragment thereof; and
(c) optionally, a recombinant HSV-2 glycoprotein D (gD) or immunogenic fragment thereof,
wherein said gC fragment consists of amino acids 27-426 of SEQ ID NO: 4 or a homolog thereof from another HSV-2 strain; and wherein said immunogenic composition does not comprise HSV-2 glycoprotein B (gB).

### Claim 28 (depends on 27)

The immunogenic composition of claim 27, wherein said adjuvant comprises a CpG-containing nucleotide molecule, an aluminum salt adjuvant, or a combination thereof.

### Claim 29 (depends on 27)

The immunogenic composition of claim 27, wherein said gE fragment consists of amino acids 24-224 or 24-409 of SEQ ID NO: 6.

### Claim 30 (depends on 27)

A method of inducing an anti-Herpes Simplex Virus (HSV) immune response in a subject, the method comprising the step of administering to said subject the immunogenic composition of claim 27.

### Claim 31 (depends on 30)

The method of claim 30, wherein said immunogenic composition is administered intramuscularly.

### Claim 32 (depends on 30)

The method of claim 30, wherein said immunogenic composition is administered before exposure to HSV.

### Claim 33 (depends on 30)

The method of claim 30, further comprising the step of administering to said subject a booster immunization.

### Claim 34 (depends on 27)

A method of treating, inhibiting, or reducing an incidence of a Herpes Simplex Virus (HSV) infection in a subject comprising the step of administering to said subject the immunogenic composition of claim 27.

### Claim 35 (depends on 34)

The method of claim 34, wherein said HSV infection is an HSV-1 infection.

### Claim 36 (depends on 34)

The method of claim 34, wherein said HSV infection is an HSV-2 infection.

### Claim 37 (depends on 34)

The method of claim 34, wherein said HSV infection is a genital HSV infection.

### Claim 38 (depends on 34)

The method of claim 34, wherein said immunogenic composition is administered intramuscularly.

### Claim 39 (depends on 34)

The method of claim 34, wherein said immunogenic composition is administered before exposure to HSV.

### Claim 40 (depends on 34)

The method of claim 34, wherein said HSV infection is a primary HSV infection.