Vaccines using nucleic acid-lipid complexes

Abstract

This invention relates to a vaccine and a method for immune activation which is effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in a mammal. The method is particularly effective for protecting a mammal from a disease including cancer, a disease associated with allergic inflammation, an infectious disease, or a condition associated with a deleterious activity of a self-antigen. Also disclosed are therapeutic compositions useful in such a method.

What is claimed is:  
     
         1 . A vaccine comprising: 
 a. at least one immunogen for vaccinating a mammal;    b. a liposome; and    c. an isolated nucleic acid molecule that does not express said immunogen of (a);    wherein said immunogen and said isolated nucleic acid molecule are complexed to or within said liposome.    
     
     
         2 . The vaccine of  claim 1 , wherein said immunogen comprises at least one epitope that elicits a cellular or humoral immune response in a mammal.  
     
     
         3 . The vaccine of  claim 1 , wherein said immunogen is a peptide.  
     
     
         4 . The vaccine of  claim 1 , wherein said immunogen is selected from the group consisting of a tumor antigen, an infectious disease pathogen antigen, an allergen and a self-antigen.  
     
     
         5 . The vaccine of  claim 1 , wherein said immunogen is a disrupted cell.  
     
     
         6 . The vaccine of  claim 1 , wherein said immunogen is a cell.  
     
     
         7 . The vaccine of  claim 6 , wherein said cell is a pathogenic microorganism.  
     
     
         8 . The vaccine of  claim 1 , wherein said vaccine comprises multiple immunogens.  
     
     
         9 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is an oligonucleotide.  
     
     
         10 . The vaccine of  claim 9 , wherein said oligonucleotide contains a CpG motif that is immunogenic in a mammal.  
     
     
         11 . The vaccine of  claim 9 , wherein said oligonucleotide is demethylated.  
     
     
         12 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is a plasmid vector that does not contain a gene insert.  
     
     
         13 . The vaccine of  claim 1 , wherein said liposome is a multilamellar vesicle.  
     
     
         14 . The vaccine of  claim 1 , wherein said liposome comprises cationic liposomes.  
     
     
         15 . The vaccine of  claim 14 , wherein said cationic liposomes have been formulated into multilamellar vesicles (MLVs).  
     
     
         16 . The vaccine of  claim 15 , wherein said liposome further comprises cholesterol complexed with said cationic lipids.  
     
     
         17 . The vaccine of  claim 1 , wherein said liposome comprises pairs of lipids selected from the group consisting of DOTMA and cholesterol; DOTAP and cholesterol; DOTIM and cholesterol; and DDAB and cholesterol.  
     
     
         18 . The vaccine of  claim 1 , further comprising a pharmaceutically acceptable excipient.  
     
     
         19 . The vaccine of  claim 18 , wherein said pharmaceutically acceptable excipient is 5-10% sucrose.  
     
     
         20 . The vaccine of  claim 1 , wherein said composition has a nucleic acid to lipid ratio of from about 1:1 to about 1:64.  
     
     
         21 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule encodes a cytokine, said nucleic acid sequence being operatively linked to a transcription control sequence.  
     
     
         22 . The vaccine of  claim 21 , wherein said cytokine is selected from the group consisting of hematopoietic growth factors, interleukins, interferons, immunoglobulin superfamily molecules, tumor necrosis factor family molecules and chemokines.  
     
     
         23 . The vaccine of  claim 21 , wherein said cytokine is an interleukin.  
     
     
         24 . The vaccine of  claim 21 , wherein said cytokine is selected from the group consisting of interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-18 (IL-18), and interleukin-15 (IL-15).  
     
     
         25 . The vaccine of  claim 1 , wherein said vaccine further comprises at least one cytokine.  
     
     
         26 . The vaccine of  claim 25 , wherein said cytokine is selected from the group consisting of hematopoietic growth factors, interleukins, interferons, immunoglobulin superfamily molecules, tumor necrosis factor family molecules and chemokines.  
     
     
         27 . The vaccine of  claim 25 , wherein said cytokine is selected from the group consisting of interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-18 (IL-18), and interleukin-15 (IL-15).  
     
     
         28 . A method to elicit a systemic, immunogen-specific immune response in a mammal, comprising administering to said mammal a vaccine comprising: 
 a. at least one immunogen for vaccinating a mammal;    b. a liposome; and    c. an isolated nucleic acid molecule that does not express said immunogen of (a);    wherein said immunogen and said isolated nucleic acid molecule are complexed to or within said liposome.    
     
     
         29 . The method of  claim 28 , wherein said step of administering is by a route selected from the group consisting of intravenous, intraperitoneal, subcutaneous, intradermal, intranodal, intramuscular, transdermal, inhaled, intranasal, rectal, vaginal, urethral, topical, oral, intraocular, intraarticular, intracranial, and intraspinal.  
     
     
         30 . The method of  claim 28 , wherein said step of administering is by a combination of intravenous and intranodal administration.  
     
     
         31 . The method of  claim 28 , wherein said step of administering is by a combination of intraperitoneal and intranodal administration.  
     
     
         32 . The method of  claim 28 , wherein said step of administering is by a combination of intradermal and intranodal administration.  
     
     
         33 . The method of  claim 28 , wherein said immunogen is administered at a dose of from about 1 μg per individual mammal to about 1 mg per individual mammal.  
     
     
         34 . The method of  claim 28 , wherein said immunogen is administered at a dose of from about 1 μg per individual mammal to about 100 μg per individual mammal.  
     
     
         35 . The method of  claim 28 , wherein said immunogen is administered at a dose of from about 1 μg per individual mammal to about 10 μg per individual mammal.  
     
     
         36 . The method of  claim 28 , wherein administration of said vaccine to said mammal produces a result selected from the group consisting of immunization against said disease or condition and stimulation of effector cell immunity against said disease or condition.