Nucleic acid vaccines

Abstract

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines (NAVs) comprising polynucleotide molecules encoding one or more antigens.

1 . A nucleic acid vaccine, comprising:
 one or more RNA polynucleotides having an open reading frame encoding an antigenic polypeptide, formulated in a cationic lipid nanoparticle having a molar ratio of about 20-60% cationic lipid: about 5-25% non-cationic lipid: about 25-55% sterol; and about 0.5-15% PEG-modified lipid.   
     
     
         2 . The vaccine of  claim 1 , wherein the cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. 
     
     
         3 . (canceled) 
     
     
         4 . The vaccine of  claim 2 , wherein the cationic lipid nanoparticle has a molar ratio of about 20-60% cationic lipid: about 5-25% non-cationic lipid: about 25-55% sterol; and about 0.5-15% PEG-modified lipid. 
     
     
         5 - 8 . (canceled) 
     
     
         9 . The vaccine of  claim 1 , wherein the antigenic polypeptide is derived from an infectious agent. 
     
     
         10 . (canceled) 
     
     
         11 . The vaccine of  claim 1 , wherein the one or more RNA polynucleotides encode a further antigenic polypeptide. 
     
     
         12 . The vaccine of  claim 1 , wherein the one or more RNA polynucleotides comprise at least one chemical modification. 
     
     
         13 . The vaccine of  claim 1 , wherein the antigenic polypeptide is selected from those proteins listed in Tables 6-14, Tables 29-30, or antigenic fragments thereof. 
     
     
         14 . The vaccine of  claim 1 , wherein the open reading frame of the one or more RNA polynucleotides encodes an antigenic polypeptide selected from Tables 6-11, Tables 22-23, or antigenic fragments thereof. 
     
     
         15 - 28 . (canceled) 
     
     
         29 . The vaccine of  claim 1 , wherein the nucleic acid vaccine is multivalent. 
     
     
         30 - 36 . (canceled) 
     
     
         37 . A nucleic acid vaccine, comprising:
 one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, formulated within a nanoparticle, wherein the nanoparticle has a mean diameter of 50-200 nm.   
     
     
         38 . The vaccine of  claim 37 , wherein the nanoparticle has a polydiversity value of less than 0.4. 
     
     
         39 . The vaccine of  claim 37 , wherein the nanoparticle has a net neutral charge at a neutral pH. 
     
     
         40 . (canceled) 
     
     
         41 . The vaccine of  claim 37 , wherein the nanoparticle is a cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. 
     
     
         42 . (canceled) 
     
     
         43 . A nucleic acid vaccine, comprising:
 one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein at least 80% of the uracil in the open reading frame have a chemical modification.   
     
     
         44 . The vaccine of  claim 43 , wherein 100% of the uracil in the open reading frame have a chemical modification. 
     
     
         45 - 131 . (canceled)