Method to Enhance an Immune Response of Nucleic Acid Vaccination

Abstract

A composition comprising liposomes associated with a nucleic acid operatively encoding an antigenic protein and with an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein, and wherein the nucleic acid and said assistor protein are associated with the same liposomes is described. The composition provides an improved immune response compared to mixtures of liposomes some of which are associated with the nucleic acid and some of which are associated with the assistor protein.

1 . A process for forming a liposomal composition comprising:
 (a) providing an aqueous suspension of small unilamellar (SUVs) formed of liposome forming materials;   (b) contacting the aqueous suspension of SUVs with nucleic acid which operatively encodes an antigenic protein to form an SUV-nucleic acid suspension;   (c) dehydrating the SUV-nucleic acid suspension to provide a dehydrated mixture: and   (d) rehydrating the dehydrated mixture in an aqueous resuspending medium to form a suspension of nucleic acid containing liposomes;   Including the step of introducing an assistor protein whereby the nucleic acid containing liposomes are associated with said assistor protein.   
     
     
         2 . The process according to  claim 1 , wherein the assistor protein is contacted with the aqueous suspension of SUV's before, during or after step b and before step c. 
     
     
         3 . The process according to  claim 1 , wherein the assistor protein is present in the resuspending medium. 
     
     
         4 . The process according to  claim 1 , wherein the liposome forming materials comprise at least one phospholipid and at least one sterol. 
     
     
         5 . The process according to  claim 1 , wherein the materials comprise at least one cationic compound and the liposomes have an overall cationic charge. 
     
     
         6 . The process according to  claim 1 , wherein the weight ratio of nucleic acid to liposome forming materials is in the range 1:100 to 1:1000. 
     
     
         7 . The process according to  claim 6 , wherein the weight ratio of nucleic acid to liposome forming materials is in the range of 1:100 to 1:300. 
     
     
         8 . The process according to  claim 1 , wherein the weight ratio of nucleic acid to assistor protein is in the range of 1000:1 to 1:1. 
     
     
         9 . The process according to  claim 8 , wherein the weight ratio of nucleic acid to assistor protein is in die range of 30:1 to 5:1. 
     
     
         10 . The process according to  claim 1 , wherein the dehydration is by freeze-drying. 
     
     
         11 . The process according to  claim 1 , wherein step (b) further comprises contacting the aqueous suspension of SUVs with a second nucleic acid which operatively encodes a second antigenic protein; and the step of introducing an assistor protein further comprises introducing a second assistor protein whereby the nucleic acid containing liposomes are associated with said second assistor protein.