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.

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, allergen, and a self-antigen. 
     
     
         5 . The vaccine of  claim 1 , wherein said vaccine comprises multiple immunogens. 
     
     
         6 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is an oligonucleotide. 
     
     
         7 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule contains a CpG motif that is immunogenic in a mammal. 
     
     
         8 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is demethylated. 
     
     
         9 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is non-coding DNA. 
     
     
         10 . The vaccine of  claim 1 , wherein said isolated nucleic acid molecule is a plasmid vector that does not contain a gene insert. 
     
     
         11 . The vaccine of  claim 1 , wherein said liposome is a multilamellar vesicle. 
     
     
         12 . The vaccine of  claim 1 , wherein said liposome comprises cationic liposomes. 
     
     
         13 . The vaccine of  claim 12 , wherein said cationic liposomes have been formulated into multilamellar vesicles (MLVs). 
     
     
         14 . The vaccine of  claim 13 , wherein said liposome further comprises cholesterol complexed with said cationic lipids. 
     
     
         15 . 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. 
     
     
         16 . The vaccine of  claim 1 , further comprising a pharmaceutically acceptable excipient. 
     
     
         17 . The vaccine of  claim 16 , wherein said pharmaceutically acceptable excipient is 5-10% sucrose. 
     
     
         18 . The vaccine of  claim 1 , wherein said composition has a nucleic acid to lipid ratio of from about 1:1 to about 1:64. 
     
     
         19 . A vaccine comprising:
 a. an antigen;   b. a liposome; and   c. a non-coding DNA molecule;   wherein said antigen and said non-coding DNA molecule are complexed to or within said liposome.   
     
     
         20 . 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 antigen of (a);   wherein said antigen and said isolated nucleic acid molecule are complexed to or within said liposome.   
     
     
         21 . The method of  claim 20 , 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. 
     
     
         22 . The method of  claim 20 , wherein said step of administering is by a combination of intravenous and intranodal administration. 
     
     
         23 . The method of  claim 20 , wherein said step of administering is by a combination of intraperitoneal and intranodal administration. 
     
     
         24 . The method of  claim 20 , wherein said step of administering is by a combination of intradermal and intranodal administration. 
     
     
         25 . The method of  claim 20 , wherein said antigen is administered at a dose of from about 1 μg per individual mammal to about 1 mg per individual mammal. 
     
     
         26 . The method of  claim 20 , wherein said antigen is administered at a dose of from about 1 μg per individual mammal to about 100 μg per individual mammal. 
     
     
         27 . The method of  claim 20 , wherein said antigen is administered at a dose of from about 1 μg per individual mammal to about 10 μg per individual mammal. 
     
     
         28 . The method of  claim 20 , 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.