Zoonotic disease rna vaccines

Abstract

The disclosure relates to Lassa virus, Nipah virus, and betacoronavirus ribonucleic acid vaccines as well as methods of using the vaccines and compositions comprising the vaccines.

1 .- 63 . (canceled) 
     
     
         64 . A method, comprising administering to a subject a messenger ribonucleic acid (mRNA) vaccine composition in an effective amount to induce an immune response to a Nipah virus protein, wherein the vaccine composition comprises:
 (a) an mRNA comprising an open reading frame (ORF) encoding a fusion protein, wherein the fusion protein comprises a Nipah virus F protein and a Nipah virus G protein; and   (b) a lipid nanoparticle,   wherein the lipid nanoparticle comprises 45-55 mol % ionizable lipid, 5-25 mol % neutral lipid, 35-45 mol % sterol, and 0.5-5 mol % polyethylene glycol (PEG)-modified lipid, wherein the ionizable lipid is a compound of Formula (I):   
       
         
           
           
               
               
           
         
          and wherein R 1  is R″M′R′ or C 5-20  alkenyl; 
         R 2  and R 3  are each independently selected from C 1-14  alkyl and C 2-14  alkenyl; 
         R 4  is —(CH 2 ) n Q, wherein Q is OH and n is selected from 3, 4, and 5; 
         M and M′ are each independently —OC(O)— or —C(O)O—; 
         R 5 , R 6 , and R 7  are each H; 
         R′ is a linear C 1-12  alkyl, or C 1-12  alkyl substituted with C 6-9  alkyl; 
         R″ is C 3-14  alkyl; 
         m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13. 
       
     
     
         65 . The method of  claim 64 , wherein:
 R 1  is R″M′R′;   R 2  and R 3  are each independently C 1-14  alkyl;   R 4  is —(CH 2 ) n Q, wherein Q is OH and n is 4;   M and M′ are each independently —OC(O)—;   R 5 , R 6 , and R 7  are each H;   R′ is C 1-12  alkyl substituted with C 6-9  alkyl;   R″ is C 3-14  alkyl; and   m is 6.   
     
     
         66 . The method of  claim 64 , wherein:
 R 1  is C 5-20  alkenyl;   R 2  and R 3  are each independently C 1-14  alkyl;   R 4  is —(CH 2 ) n Q, wherein Q is OH and n is 3;   M is —C(O)O—;   R 5 , R 6 , and R 7  are each H; and   m is 6.   
     
     
         67 . The method of  claim 64 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         68 . The method of  claim 64 , wherein the sterol is cholesterol. 
     
     
         69 . The method of  claim 64 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). 
     
     
         70 . The method of  claim 64 , wherein the PEG-modified lipid is PEG-DMG. 
     
     
         71 . The method of  claim 64 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG. 
     
     
         72 . The method of  claim 65 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG. 
     
     
         73 . The method of  claim 66 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG. 
     
     
         74 . The method of  claim 67 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG. 
     
     
         75 . The method of  claim 64 , wherein the ORF comprises chemically-modified uracil residues. 
     
     
         76 . The method of  claim 75 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine. 
     
     
         77 . The method of  claim 65 , wherein the ORF comprises chemically-modified uracil residues. 
     
     
         78 . The method of  claim 77 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine. 
     
     
         79 . The method of  claim 66 , wherein the ORF comprises chemically-modified uracil residues. 
     
     
         80 . The method of  claim 79 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine. 
     
     
         81 . The method of  claim 67 , wherein the ORF comprises chemically-modified uracil residues. 
     
     
         82 . The method of  claim 81 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine. 
     
     
         83 . The method of  claim 64 , wherein the Nipah virus F protein of the fusion protein comprises an amino acid sequence that has at least 90% identity with the amino acid sequence of SEQ ID NO: 13, and the Nipah virus G protein of the fusion protein comprises an amino acid sequence that has at least 90% identity with the amino acid sequence of SEQ ID NO: 11. 
     
     
         84 . The method of  claim 64 , wherein the effective amount is 20 μg-200 μg of the mRNA. 
     
     
         85 . The method of  claim 84 , wherein the effective amount is 50 μg-100 μg of the mRNA. 
     
     
         86 . The method of  claim 64 , wherein the vaccine composition is administered by intramuscular injection. 
     
     
         87 . The method of  claim 65 , wherein the vaccine composition is administered by intramuscular injection. 
     
     
         88 . The method of  claim 66 , wherein the vaccine composition is administered by intramuscular injection. 
     
     
         89 . The method of  claim 67 , wherein the vaccine composition is administered by intramuscular injection.