SARS vaccine compositions and methods of making and using them

• US 8,506,968 B2
• Filed: 12/28/2009
• Issued: 08/13/2013
• Est. Priority Date: 06/29/2000
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company, Lipid Sciences, Inc.
• Original Assignee: Eli Lilly and Company
• Inventors: Akeefe, Hassibullah, Kitabwalla, Moiz
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US12/655,299
• Publication Number:
  US 20110150929A1
• Time in Patent Office: 1,324 Days
• Field of Search: None
• US Class Current: 424/221.1
• 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 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2730/10022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• 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 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• 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 2770/20062 by genetic engineering
• 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 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 such as SARS, 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 a coronavirus, wherein the modified, partially delipidated viral particle of the coronavirus

is immunogenic,

is of reduced infectivity as compared to the coronavirus 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 coronavirus not subjected to delipidation,

wherein the modified, partially delipidated viral particle is produced by exposing the coronavirus not subjected to delipidation to a partial delipidation process consisting essentially of treating the coronavirus with 0.01% to 3% solvent,

and wherein the solvent is an ether, a fluoroether, an alcohol, or a combination thereof.

2. A composition comprising a modified, partially delipidated viral particle of a coronavirus, wherein the modified, partially delipidated viral particle of the coronavirus

is immunogenic,

is of reduced infectivity as compared to the coronavirus 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 coronavirus not subjected to delipidation,

wherein the modified, partially delipidated viral particle is produced by exposing the coronavirus not subjected to delipidation to a partial delipidation process consisting essentially of treating the coronavirus with 0.01% to 3% solvent, wherein the solvent is a combination of a surfactant and the ether, the fluoroether, the alcohol or the combination thereof.

3. The composition of claim 2, wherein the ether is diisopropyl ether and the alcohol is butanol.

4. The composition of claim 2, wherein the fluoroether is sevoflurane.

5. The composition of claim 2, wherein the surfactant is polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether.

6. The composition of claim 2, wherein the ether is diisopropyl ether and the surfactant is polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether.

7. The composition of claim 2, wherein the solvent is a combination of

a surfactant, an alcohol and an ether,

a surfactant, an alcohol and a fluoroether,

an alcohol and a surfactant,

an ether and a surfactant, or

an alcohol, an ether and a surfactant.

8. A method of creating a modified, partially delipidated viral particle of a coronavirus comprising the steps of:

receiving a coronavirus in a fluid,

exposing the coronavirus to a delipidation process, consisting essentially of treating the coronavirus with 0.01% to 3% solvent,

wherein the solvent is an ether, a fluoroether, an alcohol, a combination thereof, or a combination of a surfactant and the ether, the fluoroether, the alcohol or the combination thereof, and

wherein the delipidation process decreases the lipid content of a viral envelope of the coronavirus.

9. The method of claim 8, wherein the ether is diisopropyl ether and the alcohol is butanol.

10. The method of claim 8, wherein the fluoroether is sevoflurane.

11. The method of claim 8, wherein the surfactant is polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether.

12. The method of claim 8, wherein the ether is diisopropyl ether and the surfactant is polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether.

13. The method of claim 8, wherein the combination thereof is an alcohol and an ether, an alcohol and a fluoroether, an alcohol and a surfactant, an ether and a surfactant, or an alcohol, an ether and a surfactant.

14. A method of inducing an immune response to a coronavirus in an animal or a human comprising:

removing blood containing the coronavirus from the animal or the human;

obtaining plasma from the blood, the plasma containing the coronavirus;

delipidating the coronavirus by a process consisting essentially of contacting the plasma containing the coronavirus with a 0.01% to 3% solvent capable of extracting lipid from the coronavirus to produce modified, partially delipidated viral particles of the coronavirus,

wherein the solvent is an ether, a fluoroether, an alcohol, a combination thereof, or a combination of a surfactant and the ether, the fluoroether, the alcohol or the combination thereof,

wherein the modified, partially delipidated particles are of reduced infectivity and reduced lipid content as compared to the coronavirus 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 coronavirus to produce the modified, partially delipidated coronavirus viral particles;

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

administering the modified, partially delipidated viral particles of the coronavirus to the animal or the human in an amount sufficient to produce a cellular immune response or an antibody response to the coronavirus in the animal or the human.

15. The method of claim 14, wherein the combination thereof is an alcohol and an ether, an alcohol and a fluoroether, an alcohol and a surfactant, an ether and a surfactant, or an alcohol, an ether and a surfactant.