Modified Viral Particles with Immunogenic Properties and Reduced Lipid Content Useful for Treating and Preventing Infectious Diseases

• US 20080267997A1
• Filed: 05/09/2008
• Published: 10/30/2008
• Est. Priority Date: 06/29/2000
• Status: Abandoned Application

• Current Assignee: Eli Lilly and Company
• Original Assignee: Lipid Sciences, Inc.
• Inventors: Maltais, Jo-Ann B., Cham, Bill E., Bellotti, Marc
• Application Number:
  US12/118,335
• Publication Number:
  US 20080267997A1
• Time in Patent Office: Days
• US Class Current: 424/225.1
• 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

1-69. -69. (canceled)

70. A method of providing protection in a patient against an infectious hepatitis viral particle comprising the step of:

administering to the patient an effective amount of a vaccine composition comprising at least a partially delipidated hepatitis viral particle having at least one exposed viral antigen that was not exposed in a non-delipidated hepatitis viral particle, wherein the amount is effective to provide a protective effect against infection by the infectious hepatitis viral particle in the patient.

71. The method of claim 70, further comprising administering a pharmaceutically acceptable carrier or an immunostimulant.

72. The method of claim 70, wherein the protective effect comprises enhanced interferon gamma production by T cells of the patient.

73. The method of claim 72, wherein the T-cells are CD4+ or CD8+ T-cells.

74. The method of claim 70, wherein the protective effect comprises proliferation of cells of the immune system of the patient.

75. The method of claim 70, wherein the partially delipidated hepatitis viral particle has a lower cholesterol content than the non-delipidated hepatitis viral particle.

76. The method of claim 75, wherein the lower cholesterol content is at least 20% lower than the non-delipidated viral particle.

77. The method of claim 75, wherein the lower cholesterol content is at least 30% lower than the non-delipidated viral particle.

78. The method of claim 70, wherein the vaccine composition comprises partially delipidated viral particles from one or more strains of hepatitis virus or one or more types of hepatitis virus.

79. The method of claim 70, wherein the partially delipidated hepatitis viral particle has a different buoyant density than the non-delipidated hepatitis viral particle.

80. A method for provoking a positive immune response in patient having a plurality of lipid-containing hepatitis viral particles, comprising the steps of:

obtaining a fluid containing the lipid-containing hepatitis viral particles from the patient;

contacting the fluid containing the lipid-containing hepatitis viral particles with a first organic solvent capable of extracting lipid from the lipid-containing hepatitis viral particles;

mixing the fluid and the first organic solvent;

permitting organic and aqueous phases to separate;

collecting the aqueous phase containing modified hepatitis viral particles with reduced lipid content; and

introducing the aqueous phase containing the modified hepatitis viral particles with reduced lipid content into the patient wherein the modified hepatitis viral particles with reduced lipid content provoke an immune response in the patient.

81. The method of claim 80, further comprising:

contacting the aqueous phase with charcoal capable of removing the first organic solvent from the aqueous phase.

82. The method of claim 80, wherein after the aqueous phase is collected, the aqueous phase is contacted with charcoal capable of removing the first organic solvent from the aqueous phase, and the aqueous phase containing reduced levels of the first organic solvent is eluted from the charcoal before introducing the aqueous phase containing the modified hepatitis viral particles with reduced lipid content into the patient.

83. The method of claim 80, wherein the first organic solvent is an alcohol, an ether, an amine, a hydrocarbon, an ester, a surfactant, or a combination thereof.

84. The method of claim 80, wherein the first organic solvent is an alcohol, an ether, or a combination thereof.

85. The method of claim 80, wherein the ether is a C4 to C8 ether and the alcohol is a C1 to C8 alcohol.

86. The method of claim 80, wherein the fluid is plasma, serum, peritoneal fluid, lymphatic fluid, pleural fluid, pericardial fluid, cerebrospinal fluid, or a fluid of the reproductive system.

87. A method for treating a hepatitis viral infection in a patient comprising:

removing blood containing a plurality of lipid-containing infectious hepatitis viral particles from the animal or the human;

obtaining plasma from the blood, the plasma containing the lipid-containing infectious hepatitis viral particles;

contacting the plasma containing the lipid-containing infectious hepatitis viral particles with a first organic solvent capable of extracting lipid from the lipid-containing infectious hepatitis viral particles to produce modified hepatitis viral particles having reduced lipid content;

mixing the plasma and the first organic solvent;

permitting organic and aqueous phases to separate;

collecting the aqueous phase containing the modified hepatitis viral particles; and

introducing the aqueous phase containing the modified hepatitis viral particles into the patient wherein the modified hepatitis viral particles have at least one exposed viral antigen that was not exposed in the plurality of lipid-containing infectious hepatitis viral particles.

88. The method of claim 87, wherein after the aqueous phase is collected, the aqueous phase is contacted with a charcoal capable of removing the first organic solvent from the aqueous phase and aqueous phase with reduced levels of first organic solvent is eluted from the charcoal before introducing the aqueous phase containing the modified hepatitis viral particles into the patient.

89. The method of claim 87, wherein the first organic solvent is an alcohol, an ether, an amine, a hydrocarbon, an ester, a surfactant or a combination thereof.

90. The method of claim 87, wherein the first organic solvent is an alcohol, an ether, or a combination thereof.

91. The method of claim 87, wherein the ether is a C4 to C8 ether and the alcohol is a C1 to C8 alcohol.