Nucleic acid vaccine composition comprising a lipid formulation, and method of increasing the potency of nucleic acid vaccines

Abstract

A nucleic acid vaccine composition comprising one or more of a plasmid-based nucleic acid vaccine and immunotherapy, as well as a lipid formulation, is provided. In addition, the present invention provides a method of enhancing the potency of plasmid-based DNA vaccines and immunotherapies, by formulating a vaccine and/or immunotherapy in a lipid formulation, which is stable when refrigerated or stored frozen, is then delivered to a vaccinee by either needle/syringe, jet injection, or microneedles. The lipid formulation of the present invention comprises one or more lipid excipients selected from 1,2-Distearoyl-sn-glycero-3-phosphocholine, Cholest-5-en-3β-ol, 1,2-Dimyristoyl-rac-glycero-3-methylpolyoxyethlene, and or more symmetric ionizable cationic lipids. The present invention increases vaccine potency dramatically. It was unexpectedly discovered that the level of immunogen, or immune response molecules, produced in vivo is increased (versus administering merely the vaccine or immunotherapy) and, in the case of a vaccine immunogen, the immune response is enhanced.

1 . A nucleic acid vaccine composition comprising a lipid formulation, and vaccine immunogens or immune response molecules, wherein the lipid formulation comprises at least one symmetric ionizable cationic lipid selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         2 . The nucleic acid vaccine composition of  claim 1 , wherein the lipid formulation further comprises one or more lipid excipients selected from the group consisting of 1,2-Distearoyl-sn-glycero-3-phosphocholine, Cholest-5-en-3β-ol, and 1,2-Dimyristoyl-rac-glycero-3-methylpolyoxyethlene. 
     
     
         3 . The nucleic acid vaccine composition of  claim 1 , wherein the nucleic acid vaccine is a plasmid-based DNA vaccine. 
     
     
         4 . The nucleic acid vaccine composition of  claim 1 , wherein the nucleic acid vaccine is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines. 
     
     
         5 . A method of enhancing the potency of plasmid-based DNA vaccines and immunotherapies, by formulating a vaccine and/or immunotherapy in a lipid formulation comprising a symmetric ionizable cationic lipid selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5 , wherein the lipid formulation further comprises one or more lipid excipients selected from the group consisting of 1,2-Distearoyl-sn-glycero-3-phosphocholine, Cholest-5-en-3β-ol, and 1,2-Dimyristoyl-rac-glycero-3-methylpolyoxyethlene. 
     
     
         7 . The method of  claim 5 , wherein the plasmid-based DNA vaccine or immunotherapy is a plasmid-based DNA vaccine. 
     
     
         8 . The method of  claim 5 , wherein the plasmid-based DNA vaccine or immunotherapy is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines. 
     
     
         9 . The nucleic acid vaccine composition of  claim 2 , wherein the nucleic acid vaccine is a plasmid-based DNA vaccine. 
     
     
         10 . The nucleic acid vaccine composition of  claim 2 , wherein the nucleic acid vaccine is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines. 
     
     
         11 . The nucleic acid vaccine composition of  claim 3 , wherein the nucleic acid vaccine is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines. 
     
     
         12 . The method of  claim 6 , wherein the plasmid-based DNA vaccine or immunotherapy is a plasmid-based DNA vaccine. 
     
     
         13 . The method of  claim 6 , wherein the plasmid-based DNA vaccine or immunotherapy is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines. 
     
     
         14 . The method of  claim 7 , wherein the plasmid-based DNA vaccine or immunotherapy is selected from the group consisting of hantavirus vaccines including those targeting Andes virus, Sin Nombre virus, Hantaan virus, and Puumala virus; South American arenavirus vaccines including those targeting Junin virus, Machup virus, Guanarito virus, and Sabia virus; poxvirus DNA vaccines, alphavirus DNA vaccines, filovirus DNA vaccines, and Zika virus DNA vaccines.