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′ UTR 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′ UTR that comprises the sequence of SEQ ID NO: 13.   
     
     
         98 . The composition of  claim 97 , wherein the hMPV mRNA comprises the sequence of SEQ ID NO: 14. 
     
     
         99 . The composition of  claim 97 , wherein the hMPV mRNA comprises a 7mG(5′)ppp(5′)NlmpNp cap. 
     
     
         100 . The composition of  claim 97 , wherein the hMPV mRNA comprises a polyA tail. 
     
     
         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 102 , wherein 100% of uracil in the open reading frame of the hMPV mRNA comprise a 1-methylpseudouridine. 
     
     
         104 . The composition of  claim 97 , comprising 25 μg-200 μg of the hMPV mRNA. 
     
     
         105 . The composition of  claim 97 , further comprising mRNA encoding a respiratory syncytial virus (RSV) antigen. 
     
     
         106 . The composition of  claim 97 , wherein the composition further comprises lipid nanoparticles that comprise 1-5 mol % PEG-modified lipid; 10-20 mol % non-cationic lipid; 35-45 mol % cholesterol; and 40-50 mol % ionizable cationic lipid. 
     
     
         107 . The composition of  claim 106 , wherein the PEG-modified lipid is 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG), the non-cationic lipid is 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC), and the ionizable cationic lipid has the structure of Compound 1: 
       
         
           
           
               
               
           
         
       
     
     
         108 . A composition comprising:
 25 μg-200 μg human metapneumovirus (hMPV) messenger ribonucleic acid (mRNA) comprising the sequence of SEQ ID NO:14.   
     
     
         109 . The composition of  claim 108 , wherein the composition further comprises lipid nanoparticles that comprises 1-5 mol % 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG); 10-20 mol % 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC); 35-45 mol % cholesterol; and 40-50 mol % ionizable cationic lipid having the structure of Compound 1: 
       
         
           
           
               
               
           
         
       
     
     
         110 . The composition of  claim 109 , further comprising mRNA encoding a respiratory syncytial virus (RSV) antigen. 
     
     
         111 . A method comprising administering to a subject the composition of  claim 109  in an amount effective to induce a neutralizing antibody response against hMPV in the subject. 
     
     
         112 . A method comprising administering to a subject the composition of  claim 110  in an amount effective to induce a neutralizing antibody response against hMPV and/or RSV in the subject. 
     
     
         113 . The method of  claim 111 , wherein the subject is immunocompromised and/or has a pulmonary disease. 
     
     
         114 . The method of  claim 111 , wherein the subject is 5 years of age or younger. 
     
     
         115 . The method of  claim 111 , wherein the subject is 65 years of age or older. 
     
     
         116 . The method of  claim 111 , comprising administering to the subject at least two doses of the composition.