Modified viral particles with immunogenic properties and reduced lipid content useful for treating and preventing infectious diseases

• US 20070031923A1
• Filed: 04/10/2006
• Published: 02/08/2007
• Est. Priority Date: 06/29/2000
• Status: Active Grant

• Current Assignee: Eli Lilly and Company, Lipid Sciences, Inc.
• Original Assignee: Lipid Sciences, Inc.
• Inventors: Cham, Bill
• Granted Patent: US 7,439,052 B2
• Time in Patent Office: Days
• US Class Current: 435/69.100
• 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 is 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. The present invention employs solvents useful for extracting lipids from the lipid-containing infectious viral organism thereby creating immunogenic modified, partially delipidated viral particles with reduced infectivity. The present invention provides 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 the lipid-containing infectious viral organism or, in case of a therapeutic vaccine, to treat or alleviate infection against the lipid-containing infections 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 composition comprising a modified, partially delipidated viral particle of an immunodeficiency virus, wherein the modified, partially delipidated viral particle of the immunodeficiency virus

is immunogenic,

is of reduced infectivity as compared to the immunodeficiency virus not subjected to delipidation, and

comprises an envelope with envelope viral and host proteins and a lower lipid content as compared to an envelope in the immunodeficiency virus not subjected to delipidation.

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

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

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

5. The composition of claim 1, wherein the modified, partially delipidated viral particle contains at least 95% of immunoreactivity of MHC I, as compared to the immunodeficiency virus not subjected to delipidation.

6. The composition of claim 1, wherein the modified, partially delipidated viral particle contains at least 70% of immunoreactivity of gp41, as compared to the immunodeficiency virus not subjected to delipidation.

7. The composition of claim 1, wherein the modified, partially delipidated viral particle is produced by exposing the immunodeficiency virus not subjected to delipidation to a process comprising treating the immunodeficiency virus with 0.5% to 2.5% organic solvent.

8. The composition of claim 7, wherein the solvent is an ether, an alcohol, or a combination thereof.

9. The composition of claim 7, wherein the ether is diisopropyl ether and the alcohol is butanol.

10. A process of creating a modified, partially delipidated 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, comprising treating the immunodeficiency virus with 0.5% to 2.5% organic solvent, wherein the delipidation process decreases the lipid content of a viral envelope of the immunodeficiency virus.

11. The process of claim 10, wherein the immunodeficiency virus is SIV or HIV.

12. The process of claim 10, 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.

13. The process of claim 10, 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.

14. The process of claim 10, wherein the organic solvent is an ether, an alcohol, or a combination thereof.

15. The process of claim 14, wherein the ether is diisopropyl ether and the alcohol is butanol.

16. The process of claim 10, wherein the immunodeficiency virus is from the animal or the human.

17. A method of attenuating an infection by an immunodeficiency virus in an animal or a human comprising:

removing blood containing the immunodeficiency virus from the animal or the human;

obtaining plasma from the blood, the plasma containing the immunodeficiency virus;

delipidating the immunodeficiency virus by a process comprising contacting the plasma containing the immunodeficiency virus with a 0.5% to 2.5% organic solvent capable of extracting lipid from the immunodeficiency virus to produce modified, partially delipidated viral particles of the immunodeficiency virus,

wherein the modified, partially delipidated particles are of reduced infectivity and reduced lipid content as compared to the immunodeficiency virus not subjected to the delipidation process, and,

wherein the modified, partially delipidated particles comprise a modified viral envelope with envelope viral and host proteins,

wherein the contacting is for a time and under conditions sufficient to reduce the infectivity and the lipid content of the immunodeficiency virus to produce the modified, partially delipidated immunodeficiency viral particles;

separating the organic solvent from the modified, partially delipidated viral particles; and

administering the modified, partially delipidated viral particles of the immunodeficiency virus to the animal or the human in an amount sufficient to induce T-cell or antibody responses to the immunodeficiency virus in the animal or the human.

18. The method of claim 17, wherein the immunodeficiency virus is HIV or SIV.

19. The method of claim 17, wherein the modified, partially delipidated viral particles contain at least 70% of immunoreactivity of the envelope viral and host proteins as compared to the immunodeficiency virus particles not subjected to the delipidation process.

20. The method of claim 17, wherein the modified, partially delipidated viral particles contain at least 70% of immunoreactivity of MHC I, CD63, CD59 or gp 41 as compared to the immunodeficiency virus not subjected to the delipidation process.

21. The method of claim 17, wherein the organic solvent is an ether, an alcohol, or a combination thereof.

22. The method of claim 21, wherein the ether is diisopropyl ether and the alcohol is butanol.

23. A method of reducing viral loads of an immunodeficiency virus in an animal or a human comprising:

removing blood containing the immunodeficiency virus from the animal or the human;

obtaining plasma from the blood, the plasma containing the immunodeficiency virus;

delipidating the virus by a process comprising contacting the plasma containing the immunodeficiency virus with a 0.5% to 2.5% organic solvent capable of extracting lipid from the immunodeficiency virus to produce modified, partially delipidated viral particles of the immunodeficiency virus,

wherein the modified, partially delipidated particles are of reduced infectivity and reduced lipid content as compared to the immunodeficiency virus not subjected to the delipidation process, and

wherein the modified, partially delipidated particles comprise a modified viral envelope with envelope viral and host proteins,

wherein the contacting is for a time and under conditions sufficient to reduce the infectivity and the lipid content of the immunodeficiency virus to produce the modified, partially delipidated immunodeficiency viral particles;

separating the organic solvent from the modified, partially delipidated viral particles; and

administering the modified, partially delipidated viral particles of the immunodeficiency virus to the animal or the human in an amount sufficient to induce T-cell or antibody responses to the immunodeficiency virus in the animal or the human.

24. The method of claim 23, wherein the administering of the modified, partially delipidated immunodeficiency viral particles is performed concurrently with or following antiretroviral therapy.

25. The method of claim 23, wherein the immunodeficiency virus is HIV or SIV.