VACCINES USING NUCLEIC ACID-LIPID COMPLEXES
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.