Respiratory virus nucleic acid vaccines

Abstract

Provided herein, in some embodiments, are vaccines (and vaccination methods) that include a ribonucleic acid (RNA) polynucleotide encoding a human metapneumovirus (hMPV) F protein and a RNA polynucleotide encoding a human parainfluenza virus 3 (hPIV3) F protein.

1 - 96 . (canceled) 
     
     
         97 . A composition comprising: a human metapneumovirus (hMPV) messenger ribonucleic acid (mRNA) comprising a 5′ untranslated region that comprises the sequence of SEQ ID NO:12, an open reading frame that comprises a sequence having at least 95% identity to the sequence of SEQ ID NO:4, and a 3′ untranslated region that comprises the sequence of SEQ ID NO:13. 
     
     
         98 . The composition of  claim 97 , wherein the open reading frame comprises the sequence of SEQ ID NO: 4. 
     
     
         99 . The composition of  claim 97 , wherein the hMPV mRNA comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 14. 
     
     
         100 . The composition of  claim 99 , wherein the hMPV mRNA comprises the sequence of SEQ ID NO: 14. 
     
     
         101 . The composition of  claim 97 , wherein the hMPV mRNA comprises a chemical modification. 
     
     
         102 . The composition of  claim 101 , wherein the chemical modification is 1-methylpseudouridine. 
     
     
         103 . The composition of  claim 97 , further comprising a lipid nanoparticle. 
     
     
         104 . The composition of  claim 103 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % PEG-modified lipid. 
     
     
         105 . The composition of  claim 104 , wherein the ionizable cationic lipid comprises a compound of Formula (IA): 
       
         
           
           
               
               
           
         
       
       or a salt or isomer thereof,
 wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M 1  is a bond or M′; R 4  is unsubstituted C 1-3  alkyl, or —(CH 2 ) n Q, in which Q is OH, —NHC(S)N(R) 2 , —NHC(O)N(R) 2 , —N(R)C(O)R, —N(R)S(O) 2 R, —N(R)R 8 , —NHC(═NR 9 )N(R) 2 , —NHC(═CHR 9 )N(R) 2 , —OC(O)N(R) 2 , —N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —P(O)(OR′)O—, —S—S—, an aryl group, and a heteroaryl group; and R 2  and R 3  are independently selected from the group consisting of H, C 1-14  alkyl, and C 2-14  alkenyl. 
 
     
     
         106 . The composition of  claim 105 , wherein the compound is Compound 1: 
       
         
           
           
               
               
           
         
       
     
     
         107 . A composition comprising:
 (a) a human metapneumovirus (hMPV) messenger ribonucleic acid (mRNA) comprising a 5′ untranslated region that comprises the sequence of SEQ ID NO:12, an open reading frame that comprises the sequence of SEQ ID NO:4, and a 3′ untranslated region that comprises the sequence of SEQ ID NO:13; and   (b) a lipid nanoparticle comprising an ionizable cationic lipid, a neutral lipid, cholesterol, and a PEG-modified lipid.   
     
     
         108 . The composition of  claim 107 , wherein the hMPV mRNA comprises the sequence of SEQ ID NO: 14. 
     
     
         109 . The composition of  claim 108 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % PEG-modified lipid. 
     
     
         110 . The composition of  claim 109 , wherein the ionizable cationic lipid comprises a compound of Formula (IA): 
       
         
           
           
               
               
           
         
       
       or a salt or isomer thereof,
 wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M 1  is a bond or M′; R 4  is unsubstituted C 1-3  alkyl, or —(CH 2 ) n Q, in which Q is OH, —NHC(S)N(R) 2 , —NHC(O)N(R) 2 , —N(R)C(O)R, —N(R)S(O) 2 R, —N(R)R 8 , —NHC(═NR 9 )N(R) 2 , —NHC(═CHR 9 )N(R) 2 , —OC(O)N(R) 2 , —N(R)C(O)OR, heteroaryl or heterocycloalkyl; M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —P(O)(OR′)O—, —S—S—, an aryl group, and a heteroaryl group; and R 2  and R 3  are independently selected from the group consisting of H, C 1-14  alkyl, and C 2-14  alkenyl. 
 
     
     
         111 . The composition of  claim 110 , wherein the compound is Compound 1: 
       
         
           
           
               
               
           
         
       
     
     
         112 . The composition of  claim 111 , wherein the hMPV mRNA comprises a chemical modification. 
     
     
         113 . The composition of  claim 112 , wherein the chemical modification is 1-methylpseudouridine. 
     
     
         114 . The composition of  claim 107 , wherein the hMPV mRNA comprises a chemical modification. 
     
     
         115 . The composition of  claim 114 , wherein the chemical modification is 1-methylpseudouridine. 
     
     
         116 . A method comprising administering to a subject the composition of  claim 97  in an amount effective to induce a neutralizing antibody response against hMPV in the subject.