Virus-like particles, methods of preparation, and immunogenic compositions

• US 20060088909A1
• Filed: 05/19/2003
• Published: 04/27/2006
• Est. Priority Date: 05/17/2002
• Status: Abandoned Application

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Yao, Qizhi, Yang, Chinglai, Kang, Sang-Moo, Compans, Richard W
• Application Number:
  US10/514,462
• Publication Number:
  US 20060088909A1
• Time in Patent Office: Days
• US Class Current: 435/69.100
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2710/14143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/13023 Virus like particles [VLP]
• CPC Class Codes: C12N 2740/15022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/15023 Virus like particles [VLP]
• CPC Class Codes: C12N 2740/16023 Virus like particles [VLP]
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/12222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/12223 Virus like particles [VLP]
• CPC Class Codes: C12N 2760/14122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/14123 Virus like particles [VLP]
• CPC Class Codes: C12N 2760/20223 Virus like particles [VLP]
• CPC Class Codes: C12N 2770/20022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/20023 Virus like particles [VLP]
• CPC Class Codes: C12N 2810/60 from viruses
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Briefly described, virus-like particles, methods of preparing virus-like particles, immunogenic compositions that include virus-like particles, and methods of liciting an immune response using immunogenic compositions that include virus-like particles are described herein. A virus-like particle (VLP) can include a viral core protein that can self assemble into the VLP core and at least one viral surface envelope glycoprotein expressed on the surface of the VLP. The viral protein and the viral surface envelope glycoprotein are from different viruses. Another VLP can include a viral core protein that can self assemble into a VLP core; at least one viral surface envelope glycoprotein expressed on the surface of the VLP; and at least one adjuvant molecule expressed on the surface of the VLP.

Claims

1. A virus-like particle (VLP), comprising:

a viral core protein that can self assemble into the VLP core; and

at least one viral surface envelope glycoprotein expressed on the surface of the VLP, wherein the viral protein and the viral surface envelope glycoprotein are from different viruses.

10. An immunogenic composition, comprising the VLP of claim 1 and a pharmacologically acceptable carrier.

12. A method of generating an immunological response in a host, comprising the step of administering an effective amount of the immunogenic composition of claim 10 to the host.

14. A method of treating a condition, comprising administering to a host in need of treatment an effective amount of the immunogenic composition of claim 10.

16. A method of determining exposure of a host to a virus, said method comprising the steps of:

contacting a biological fluid of the host with a virus-like particle (VLP) selected from the VLP of claim 1, the VLP of claim 4, and combinations thereof, wherein the VLP is of the same virus type to which exposure is being determined, under conditions which are permissive for binding of antibodies in the biological fluid with the VLP; and

detecting binding of antibodies within the biological fluid with the VLP, whereby exposure of the host to the virus is determined by the detection of antibodies bound to the VLP.

17. The method of claim 16, wherein detecting includes the use of a labeled second antibody which is specific to antibodies in the biological fluid being tested.

20. The method for targeting antigen presenting cells in a host of claim 14, wherein the antigen presenting cell is a follicular dendritic cell and the at least one adjuvant molecule is a C3d adjuvant molecule.

27. A method of boosting the immunization of a host having been previously treated with a vaccine, comprising the step of administering an effective amount of the immunogenic composition of claim 10 to the host.

2. The VLP of claim 2, wherein the viral core protein is selected from a viral Gag viral core protein, an HIV Gag protein, an SIV Gag protein, an MuLV Gag viral core protein, a VSV M viral core protein, an Ebola VP40 viral core protein, corona virus M and E proteins, a Bunyavirus N Protein viral core protein, and combinations thereof.

3. The VLP of claim 2, wherein the viral surface envelope surface glycoprotein is selected from a human immunodeficiency virus (HIV), a feline immunodeficiency virus (FIV), a feline leukemia virus, a bovine immunodeficiency virus, a bovine leukemia virus, a equine infectious anemia virus, a human T-cell leukemia virus, a Bunyavirus glycoprotein, a Lassa fever virus glycoprotein, an Ebola virus glycoprotein, a corona virus glycoprotein, an arenavirus glycoprotein, a Filovirus glycoprotein, an influenza virus glycoprotein, a paramyxovirus glycoprotein, a rhabdovirus glycoprotein, an alphavirus glycoprotein, a flavivirus glycoprotein, and combinations thereof.

4. A virus-like particle (VLP), comprising:

a viral core protein that can self assemble into a VLP core;

at least one viral surface envelope glycoprotein expressed on the surface of the VLP; and

at least one adjuvant molecule expressed on the surface of the VLP.

5. The VLP of claim 4, wherein the viral core protein and the viral surface envelope glycoprotein are from different viruses.

6. The VLP of claim 4, wherein the viral core protein and the viral surface envelope glycoprotein are from the same virus.

7. The VLP of claim 4, wherein the viral core protein is selected from an HIV Gag viral core protein, an SIV Gag viral core protein, an MuLV Gag viral core protein, a VSV M viral core protein, an Ebola VP40 viral core protein, a corona virus M protein, a corona virus E protein, a Bunya Virus N Protein viral core protein, and combinations thereof.

8. The VLP of claim 4, wherein the viral surface envelope surface glycoprotein is selected from a human immunodeficiency virus (HIV), a simian-human immunodeficiency virus (SHIV), a feline immunodeficiency virus (FIV), a feline leukemia virus, a bovine immunodeficiency virus, a bovine leukemia virus, a equine infectious anemia virus, a human T-cell leukemia virus, a Bunya Virus glycoprotein, a Lassa fever virus glycoprotein, an Ebola virus glycoprotein, corona virus glycoprotein, an Arena virus glycoprotein, a Filo viruse glycoprotein, an influenza virus glycoprotein, a paramyxovirus glycoprotein, a rhabdo virus glycoprotein, an alphavirus glycoprotein, a flavi virus glycoprotein, and combinations thereof.

9. The VLP of claim 4, wherein the at least one adjuvant molecule is selected from an influenza HA adjuvant molecule, a parainfluenza HN adjuvant molecule, a Venezuelan equine encephalitis (VEE) adjuvant molecule, a F1t3 adjuvant molecule, a C3d adjuvant molecule, a mannose receptor adjuvant molecule, a CD40 adjuvant molecule, and combinations thereof.

11. An immunogenic composition, comprising the VLP of claim 4 and a pharmacologically acceptable carrier.

13. A method of generating an immunological response in a host, comprising the step of administering an effective amount of the immunogenic composition of claim 11 to the host.

15. A method of treating a condition, comprising administering to a host in need of treatment an effective amount of the immunogenic composition of claim 11.

18. A method for targeting antigen presenting cells in a host, comprising the step of administering an effective amount of the immunogenic composition of claim 11 to the host, wherein the at least one adjuvant molecule is selected from a Venezuelan equine encephalitis (VEE) adjuvant molecule, a F1t3 adjuvant molecule, a C3d adjuvant molecule, a mannose receptor adjuvant molecule, a CD40 adjuvant molecule, and combinations thereof.

19. The method for targeting antigen presenting cells in a host of claim 18, wherein the antigen presenting cell is a dendritic cell and the at least one adjuvant molecule is selected from a Venezuelan equine encephalitis (VEE) adjuvant molecule, a F1t3 adjuvant molecule, a mannose receptor adjuvant molecule, a CD40 adjuvant molecule, and combinations thereof.

21. A method for targeting mucosal surfaces in a host, comprising the step of administering an effective amount of the immunogenic composition of claim 11 to the host, wherein the at least one adjuvant molecule is selected from an influenza HA adjuvant molecule, a parainfluenza HN adjuvant molecule, and combinations thereof.

22. A method for producing humoral and cellular immune responses in mucosal and systemic compartments, comprising administering an effective amount of the immunogenic composition of claim 11 to the host, wherein the at least one viral surface envelope surface glycoprotein is selected from human immunodeficiency virus (HIV), and wherein the at least one adjuvant molecule is selected from an influenza HA adjuvant molecule, a parainfluenza HN adjuvant molecule, and combinations thereof.

28. A method of boosting the immunization of a host having been previously treated with a vaccine, comprising the step of administering an effective amount of the immunogenic composition of claim 11 to the host.

23. A method of making a virus-like particle (VLP), comprising the steps of:

providing a viral core protein expression vector;

providing a viral surface envelope surface glycoprotein expression vector;

providing a adjuvant molecule expression vector; and

introducing into a cell the viral core protein expression vector, the viral surface envelope surface glycoprotein expression vector, and the adjuvant molecule expression vector and allowing for expression of the viral surface envelope surface glycoprotein and the adjuvant molecule,

whereby the VLP is formed by the cells.

24. The method of claim 23, wherein the VLP is selected from human immunodeficiency virus (HIV) VLP, a simian-human immunodeficiency virus (SHIV) VLP, a feline immunodeficiency virus (FIV) VLP, a feline leukemia virus VLP, a bovine immunodeficiency virus VLP, a bovine leukemia virus VLP, a equine infectious anemia virus VLP, a human T-cell leukemia virus VLP, a Bunya Virus VLP, Lassa fever virus VLP, Ebola virus VLP, corona virus VLP, Arena virus VLP, Filovirus VLP, influenza virus VLP, paramyxovirus VLP, rhabdo virus VLP, alphavirus VLP, and flavi virus VLP.

25. A method of making a virus-like particle (VLP), comprising the steps of:

operably linking a coding sequence for a viral core protein of a virus to a promoter, and inserting it into a viral core protein expression vector;

operably linking a coding sequence for a viral surface envelope glycoprotein of a virus to a promoter, and inserting it into a viral surface envelope surface glycoprotein expression vector;

operably linking a coding sequence for an adjuvant molecule to a promoter, and inserting it into a adjuvant molecule expression vector;

simultaneously introducing into a cell the viral core protein expression vector, the viral surface envelope surface glycoprotein expression vector, and the adjuvant molecule expression vector and allowing for expression of the viral surface envelope surface glycoprotein and the adjuvant molecule,

whereby the VLP is formed by the cells.

26. The method of claim 25, wherein the promoter is selected from a baculovirus promoter and a recombinant modified vaccinia Ankara (MVA) promoter, a CMV promoter, EF promoter, adenovirus promoter, recombinant VSV, recombinant adenovirus, recombinant alphavirus, and recombinant DNA expression vectors.