Hmpv mrna vaccine composition

Abstract

Provided herein are vaccine composition comprising a chemically-modified messenger ribonucleic acid (mRNA) encoding a hMPV fusion (F) glycoprotein and a chemically-modified mRNA encoding a hPIV3 F glycoprotein formulated in a cationic lipid nanoparticle formulation, and related method for inducing an antigen-specific immune response.

1 - 58 . (canceled) 
     
     
         59 . A method of inducing in a human subject human metapneumovirus (hMPV) neutralizing antibody titers, the method comprising administering to the human subject a vaccine composition comprising (a) a messenger RNA (mRNA) comprising an open reading frame encoding a wild-type hMPV fusion (F) glycoprotein, wherein the mRNA comprises a nucleic acid sequence having at least 80% identity to the nucleic acid sequence of SEQ ID NO: 1, and (b) a lipid nanoparticle. 
     
     
         60 . The method of  claim 59 , wherein the vaccine composition comprises a 25 μg to 150 μg dose of the mRNA. 
     
     
         61 . The method of  claim 60 , wherein the vaccine composition comprises a 150 μg dose of the mRNA. 
     
     
         62 . The method of  claim 60 , wherein the vaccine composition comprises a 75 μg dose of the mRNA. 
     
     
         63 . The method of  claim 60 , wherein the vaccine composition comprises a 25 μg dose of the mRNA. 
     
     
         64 . The method of  claim 59 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a non-cationic lipid, a sterol, and a polyethylene glycol (PEG)-modified lipid. 
     
     
         65 . The method of  claim 64 , wherein the lipid nanoparticle comprises 45-55 mole percent (mol %) of the ionizable cationic lipid, 5-15 mol % of the non-cationic lipid, 35-45 mol % of the sterol, and 1-2 mol % of the PEG-modified lipid. 
     
     
         66 . The method of  claim 65 , wherein the ionizable cationic lipid is Compound I, the non-cationic lipid is DSPC (1,2-Distearoyl-sn-glycero-3-phosphocholine), the sterol is cholesterol, and the PEG-modified lipid is DMG-PEG (1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000), and wherein Compound I has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         67 . The method of  claim 59 , wherein the mRNA has at least 90% identity to the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         68 . The method of  claim 67 , wherein the mRNA has at least 95% identity to the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         69 . The method of  claim 68 , wherein the mRNA comprises the nucleic acid sequence of SEQ ID NO: 1. 
     
     
         70 . The method of  claim 59 , wherein the open reading frame sequence comprises the nucleic acid sequence of SEQ ID NO: 7. 
     
     
         71 . The method of  claim 59 , wherein the wild-type hMPV fusion (F) glycoprotein comprises the amino acid sequence of SEQ ID NO: 8. 
     
     
         72 . The method of  claim 59 , wherein the mRNA comprises 1-methylpseudourine. 
     
     
         73 . The method of  claim 72 , wherein the mRNA comprises 1-methylpseudourine at all uridine positions of the mRNA. 
     
     
         74 . The method of  claim 59 , wherein the mRNA comprises a 5′ cap and a polyA tail. 
     
     
         75 . The method of  claim 59 , wherein the mRNA comprises a 5′ untranslated region and a 3′ untranslated region. 
     
     
         76 . A method of inducing in a human subject human metapneumovirus (hMPV) neutralizing antibody titers, the method comprising administering to the human subject a 25 μg to 150 μg dose of a vaccine composition comprising (a) a messenger RNA (mRNA) comprising an open reading frame encoding a wild-type hMPV fusion (F) glycoprotein, wherein the mRNA comprises a nucleic acid sequence having at least 80% identity to the nucleic acid sequence of SEQ ID NO: 1, and (b) a lipid nanoparticle, and wherein the mRNA comprises 1-methylpseudourine. 
     
     
         77 . The method of  claim 76 , wherein the mRNA comprises 1-methylpseudourine at all uridine positions of the mRNA. 
     
     
         78 . The method of  claim 77 , wherein the mRNA further comprise a 5′ untranslated region, 5′ cap, a polyA tail, and 3′ untranslated region.