Method of making modified immunodeficiency virus particles

• US 7,439,052 B2
• Filed: 04/10/2006
• Issued: 10/21/2008
• Est. Priority Date: 06/29/2000
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company, Lipid Sciences, Inc.
• Original Assignee: Lipid Sciences, Inc.
• Inventors: Cham, Bill E.
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US11/401,434
• Publication Number:
  US 20070031923A1
• Time in Patent Office: 925 Days
• Field of Search: None
• US Class Current: 435/235.1
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/552 Veterinary vaccine
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2730/10034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2730/10122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2730/10162 by genetic engineering
• 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 2740/15034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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 2770/20034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/24322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/24334 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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

Described are a composition and method for reducing the occurrence and severity of infectious diseases, especially infectious diseases in which lipid-containing infectious viral organisms are found in biological fluids, such as blood. Solvents useful for extracting lipids from lipid-containing infectious viral organisms are employed thereby creating immunogenic modified, partially delipidated viral particles with reduced infectivity. Provided are delipidated viral vaccine compositions, such as therapeutic vaccine compositions, comprising these modified, partially delipidated viral particles with reduced infectivity, optionally combined with a pharmaceutically acceptable carrier or an immunostimulant. The vaccine composition is administered to a patient to provide protection against a lipid-containing infectious viral organism or, as a therapeutic vaccine, to treat or alleviate infection by the lipid-containing infectious viral organism. The vaccine compositions of the present invention include combination vaccines of modified viral particles obtained from one or more strains of a virus and/or one or more types of virus.

Claims

1. A process of creating a modified, partially delipidated immunogenic immunodeficiency viral particle of an immunodeficiency virus, comprising the steps of:

receiving an immunodeficiency virus in a fluid,

exposing the immunodeficiency virus to a delipidation process, consisting essentially of treating the immunodeficiency virus with 0.5% to 2.5% organic solvent, wherein the organic solvent is not a detergent or surfactant, wherein the delipidation process decreases the lipid content of a viral envelope of the immunodeficiency virus.

2. The process of claim 1, wherein the immunodeficiency virus is SIV or HIV.

3. The process of claim 1, wherein the modified, partially delipidated viral particle contains at least 70% of immunoreactivity of the viral and host proteins as compared to the immunodeficiency virus not subjected to the delipidation process.

4. The process of claim 1, wherein the modified, partially delipidated viral particle contains at least 70% of immunoreactivity of MHC I, CD63, CD59 or gp 41 as compared to the immunodeficiency virus not subjected to delipidation.

5. The process of claim 1, wherein the organic solvent is an ether, an alcohol, or a combination thereof.

6. The process of claim 5, wherein the ether is diisopropyl ether and the alcohol is butanol.

7. The process of claim 1, wherein the immunodeficiency virus is from an animal or a human.

8. The process of claim 1, wherein the immunodeficiency virus is HIV-1 or HIV-2.

9. The process of claim 1, wherein the fluid is a biological fluid selected from the group consisting of blood, plasma, serum, lymphatic fluid, cerebrospinal fluid, peritoneal fluid, pleural fluid, and pericardial fluid.

10. The process of claim 1, wherein the fluid is a biological fluid selected from the group consisting of blood, plasma and serum.

11. The process of claim 1, wherein the organic solvent is selected from the group consisting of hydrocarbons, ethers, alcohols, phenols, esters, halohydrocarbons, halocarbons, amines, and combinations thereof.

12. The process of claim 1, wherein the organic solvent is diisopropyl ether.

13. The process of claim 1, wherein the organic solvent is a combination of diisopropyl ether and butanol.

14. The process of claim 11, wherein the ether is a C₄-C₈ containing ether selected from the group consisting of ethyl ether, diethyl ether, propyl ether, isopropyl ether, diisopropyl ether and combinations thereof.

15. The process of claim 5, wherein the alcohol and the ether are present in a ratio of alcohol to ether of from about 0.01:

99.99 to about 60;

40.

16. The process of claim 5, wherein the alcohol and the ether are present in a ratio of alcohol to ether of from about 10:

90 to about 5;

95.

17. The process of claim 5, wherein the alcohol and the ether are present in a ratio of alcohol to ether of from about 10:

90 to about 50;

50.

18. The process of claim 5, wherein the alcohol and the ether are present in a ratio of alcohol to ether of from about 20:

80 to about 45;

55.

19. The process of claim 5, wherein the alcohol and the ether are present in a ratio of alcohol to ether of about 25:

75.

20. The process of claim 5, wherein the ether is diethyl ether and the alcohol is butanol.