Adjuvant compositions and methods for enhancing immune responses to polynucleotide-based vaccines

Abstract

The invention provides adjuvants, immunogenic compositions, and methods useful for polynucleotide-based vaccination and immune response. In particular, the invention provides an adjuvant of cytofectin:co-lipid mixture wherein cytofectin is GAP-DMORIE.

What is claimed is: 
     
         1 . A method for increasing the immune response to an allergenic reaction in a mammal comprising administering to the mammal an immunogenic composition comprising:
 (a) one or more immunogen-encoding polynucleotides, or immunogenic polypeptides or polysaccharides from the allergen, in an amount sufficient to increase the immune response in the mammal to the polynucleotides, polypeptides, or polysaccharides; and   (b) an adjuvant comprising a (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt and one or more co-lipids, wherein the immune response to the allergenic reaction is increased in the mammal.   
     
     
         2 . The method of  claim 1 , wherein the (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt is (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium bromide (GAP-DMORIE). 
     
     
         3 . The method of  claim 1 , wherein the co-lipid is a phosphatidylethanolamine. 
     
     
         4 . The method of  claim 3 , wherein the phosphatidylethanolamine is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). 
     
     
         5 . The method of  claim 3 , wherein the phosphatidylethanolamine is 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPyPE). 
     
     
         6 . The method of  claim 1 , wherein the molar ratio of (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt to co-lipid is from about 9:1 to about 1:9. 
     
     
         7 . The method of  claim 3 , wherein the phosphatidylethanolamine is 1,2-dimyristoyl-glycer-3-phosphoethanolamine (DMPE). 
     
     
         8 . The method of  claim 1 , wherein the molar ratio of (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt to co-lipid is from about 4:1 to about 1:4. 
     
     
         9 . The method of  claim 1 , wherein the molar ratio of (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt to co-lipid is from about 2:1 to about 1:2. 
     
     
         10 . The method of  claim 1 , wherein the molar ratio of (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-1-propanaminium salt to co-lipid is about 1:1. 
     
     
         11 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         12 . The method of  claim 1 , wherein the immunogenic composition further comprises an excipient. 
     
     
         13 . The method of  claim 1 , wherein the administration is intravenous. 
     
     
         14 . The method of  claim 1 , wherein the administration is by a route selected from the group consisting of intramuscular, intratracheal, intranasal, transdermal, interdermal, subcutaneous, intraocular, vaginal, rectal, intraperitoneal, intraintestinal, and inhalation. 
     
     
         15 . The method of  claim 1 , wherein the polynucleotide is DNA, RNA, or a nucleic acid oligomer from the allergen. 
     
     
         16 . The method of  claim 1 , wherein the polynucleotide is a linear or circular polynucleotide from the allergen. 
     
     
         17 . The method of  claim 1 , wherein the polynucleotide is all, or part of, a plasmid DNA from the allergen.