Modified viral particles with immunogenic properties and reduced lipid content

• US 7,407,662 B2
• Filed: 06/21/2004
• Issued: 08/05/2008
• 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: Bellotti, Marc, Maltais, Jo-Ann B., Cham, Bill E.
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US10/873,015
• Publication Number:
  US 20050032222A1
• Time in Patent Office: 1,506 Days
• Field of Search: 424/184.1, 424/204.1
• US Class Current: 424/204.1
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/29 Hepatitis virus
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C12N 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2730/10163 by chemical treatment
• 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 2740/15063 by chemical treatment
• 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 2770/24063 by chemical treatment
• 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 2770/24363 by chemical treatment
• 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

The present invention relates to a 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 modified viral particles with reduced infectivity and enhanced antigenicity. The present invention provides vaccine compositions, comprising these modified viral particles with reduced infectivity and enhanced antigenicity, 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. 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 modified viral particle comprising a partially delipidated viral particle, wherein the partially delipidated viral particle is immunodeficiency virus or coronavirus, is immunogenic and comprises an envelope with proteins and a lower lipid content as compared to an envelope in an unmodified viral particle, and wherein the lower lipid content is obtained by a process consisting essentially of treating a viral particle with an organic solvent that is not a detergent or a surfactant.

2. The modified viral particle of claim 1, wherein the modified viral particle is an HIV viral particle having a lower cholesterol content and a lower cholesterol to total protein ratio than an unmodified HIV viral particle and the lower cholesterol to total protein ratio in the modified HIV viral particle is reduced no more than 60% as compared to a cholesterol to total protein ratio in the unmodified HIV viral particle.

3. The modified viral particle of claim 1, wherein the modified viral particle is an HIV viral particle having a lower cholesterol content than an unmodified HIV viral particle and the lower cholesterol content is reduced no more than 54% as compared to a cholesterol content in the unmodified HIV viral particle.

4. The modified HIV viral particle of claim 2, wherein the cholesterol content in the modified HIV viral particle is reduced no more than 50% as compared to the unmodified HIV viral particle.

5. The modified HIV viral particle of claim 2, wherein the modified HIV viral particle has a different buoyant density than the unmodified HIV viral particle.

6. The modified viral particle of claim 1, wherein the modified viral particle is an HIV viral particle.

7. The modified viral particle of claim 6, wherein the modified HIV viral particle has reduced cholesterol content when compared to the unmodified HIV viral particle.

8. The modified viral particle of claim 6, wherein the modified HIV viral particle has p24 levels higher than 40% of p24 levels in the unmodified HIV viral particle.

28. The modified viral particle of claim 1, wherein the modified viral particle has an infectivity reduced by no more than 2.5 log units as compared to the unmodified viral particle.

9. A modified HIV viral particle comprising a partially delipidated HIV viral particle comprising:

a viral envelope with a lower cholesterol content than a cholesterol content in a viral envelope of an unmodified HIV viral particle, wherein a cholesterol to total protein ratio in the modified HIV viral particle is reduced no more than 60% as compared to a cholesterol to total protein ratio in the unmodified HIV viral particle, and,

a different buoyant density than the unmodified HIV viral particle,

wherein the lower cholesterol content is obtained by a process consisting essentially of treating an HIV viral particle with an organic solvent that is not a detergent or a surfactant.

10. The modified HIV viral particle of claim 9, wherein the modified HIV viral particle has p24 levels within at least 40% of p24 levels in the unmodified HIV viral particle.

11. The modified HIV viral particle of claim 9, wherein the cholesterol content in the modified HIV viral particle is reduced no more than 54% as compared to cholesterol content in the unmodified HIV viral particle.

14. The modified HIV viral particle of claim 9, further comprising a protein, wherein the protein is gp41, gpl120 or p24 protein.

12. A modified HIV viral particle comprising a partially delipidated HIV viral particle comprising:

a viral envelope with a lower cholesterol content than a cholesterol content in a viral envelope of an unmodified HIV viral particle, wherein the cholesterol content in the modified HIV viral particle is reduced no more than 54% as compared to a cholesterol content in the unmodified HIV viral particle,

wherein the lower cholesterol content is obtained by a process consisting essentially of treating an HIV viral particle with an organic solvent that is not a detergent or a surfactant.

13. The modified HIV viral particle of claim 12, wherein the cholesterol content in the modified viral particle is reduced no more than 50% as compared to the cholesterol content in the unmodified viral particle.

15. An antigen delivery vehicle obtained by a method comprising the steps of:

receiving a plurality of viral particles in a fluid, each viral particle having a viral envelope containing lipid, wherein the viral particles are immunodeficiency virus or coronavirus;

exposing the viral particles to a delipidation process to create modified viral particles, the delipidation process consisting essentially of treating the viral particles with 0.5% to 2.5% ether, wherein the delipidation process decreases the lipid content of the viral envelope and exposes at least one antigen,

wherein the modified viral particle comprises patient specific antigens.

16. A composition comprising at least a partially delipidated HIV viral particle comprising an envelope and having at least one exposed viral antigen that was not exposed in a non-delipidated HIV viral particle, wherein the partially delipidated viral particle is immunogenic, has a ratio of μ

g of cholesterol relative to μ

g of total protein of at least 0.06, and wherein the partially delipidated HIV viral particle is obtained by a process consisting essentially of treating an HIV viral particle with an organic solvent that is not a detergent or a surfactant.

17. The composition of claim 16, wherein the immunogenic partially delipidated HIV viral particle enhances interferon gamma production by T-cells.

18. The composition of claim 17, wherein the T-cells are CD4+ or CD8+ T-cells.

19. The composition of claim 17, wherein the immunogenic partially delipidated HIV viral particle enhances proliferation of cells of the immune system.

20. The composition of claim 16, wherein the partially delipidated HIV viral particle has a lower cholesterol content than a cholesterol content of the non-delipidated HIV viral particle.

21. The composition of claim 20, wherein the lower cholesterol content is at least 20% lower than the cholesterol content of the non-delipidated HIV viral particle.

22. The composition of claim 20, wherein the lower cholesterol content is at least 30% lower than the cholesterol content of the non-delipidated HIV viral particle.

23. The composition of claim 16, comprising partially delipidated HIV viral particles from one or more strains of HIV virus or one or more types of HIV virus.

24. The composition of claim 16, wherein the partially delipidated HIV viral particle has a different buoyant density than the non-delipidated HIV viral particle.

25. The composition of claim 16, wherein the partially delipidated HIV viral particle has reduced cholesterol content when compared to a cholesterol content of the non-delipidated HIV viral particle.

26. The composition of claim 16, wherein the partially delipidated HIV viral particle has p24 levels higher than 40% of p24 levels in the non-delipidated HIV viral particle.

27. The composition of claim 16, wherein the partially delipidated HIV viral particle comprises a protein and the protein is gp41, gp120 or p24 protein.

29. A modified viral particle comprising a partially delipidated viral particle, wherein the partially delipidated viral particle is immunodeficiency virus or coronavirus, is immunogenic and comprises an envelope with proteins and a lower lipid content as compared to an envelope in an unmodified viral particle, wherein the partially delipidated viral particle is obtained by a delipidation process consisting essentially of treating viral particles with an organic solvent which is not a detergent or a surfactant, and wherein the delipidation process decreases the lipid content of the viral envelope and exposes at least one antigen.

30. A modified HIV viral particle comprising a partially delipidated HIV viral particle, wherein the partially delipidated HIV viral particle is immunogenic and comprises an envelope with proteins and a lower lipid content as compared to an envelope in an unmodified HIV viral particle, and wherein the lower lipid content is obtained by a process consisting essentially of treating an HIV viral particle with an organic solvent that is not a detergent or a surfactant, the partially delipidated HIV viral particle having a lower cholesterol to total protein ratio than the unmodified HIV viral particle.

31. The modified HIV viral particle of claim 30, wherein the organic solvent is 0.5% to 2.5% ether.