Infectious disease vaccines

Abstract

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.

1 .- 111 . (canceled) 
     
     
         112 . A Dengue virus (DENV) messenger ribonucleic acid (mRNA) vaccine, comprising:
 an mRNA polynucleotide comprising an open reading frame encoding a DENV polypeptide; and   a lipid nanoparticle comprising 20-60 mol % cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid.   
     
     
         113 . The DENV mRNA vaccine of  claim 112 , wherein the DENV polypeptide is selected from a DENV envelope (E) protein, a DENV membrane (M) protein, a DENV precursor membrane (prM) protein, a DENV capsid (C) protein, and a DENV prME protein. 
     
     
         114 .- 165 . (canceled) 
     
     
         166 . The DENV mRNA vaccine of  claim 112 , wherein the mRNA polynucleotide comprises a chemical modification. 
     
     
         167 . The DENV mRNA vaccine of  claim 166 , wherein the chemical modification is selected from pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 5-methyluridine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine, and 2′-O-methyl uridine. 
     
     
         168 . (canceled) 
     
     
         169 . The DENV mRNA vaccine of  claim 167 , wherein the chemical modification is a N1-methylpseudouridine. 
     
     
         170 . (canceled) 
     
     
         171 . The DENV mRNA vaccine of  claim 169 , wherein 100% of the uracil in the open reading frame has a chemical modification. 
     
     
         172 .- 182 . (canceled) 
     
     
         183 . The DENV mRNA vaccine of  claim 112 , wherein the cationic lipid is an ionizable cationic lipid and the sterol is cholesterol. 
     
     
         184 .- 190 . (canceled) 
     
     
         191 . A method of inducing an immune response in a subject, the method comprising administering to the subject the DENV mRNA vaccine of  claim 112  in an amount effective to produce an antigen-specific immune response in the subject. 
     
     
         192 .- 477 . (canceled) 
     
     
         478 . A Dengue virus (DENV) messenger ribonucleic acid (mRNA) vaccine, comprising:
 an mRNA polynucleotide comprising an open reading frame encoding a DENV polypeptide; and   a lipid nanoparticle comprising 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid,   wherein 100% of the uracil in the open reading frame has a chemical modification.   
     
     
         479 . The DENV mRNA vaccine of  claim 478 , wherein the chemical modification is a N1-methylpseudouridine. 
     
     
         480 . The DENV mRNA vaccine of  claim 478 , wherein the DENV polypeptide comprises a DENV envelope (E) protein. 
     
     
         481 . The DENV mRNA vaccine of  claim 478 , wherein the DENV polypeptide comprises a DENV membrane (M) protein. 
     
     
         482 . The DENV mRNA vaccine of  claim 478 , wherein the DENV polypeptide comprises a DENV precursor membrane (prM) protein. 
     
     
         483 . The DENV mRNA vaccine of  claim 478 , wherein the DENV polypeptide comprises a DENV prME protein. 
     
     
         484 . The DENV mRNA vaccine of  claim 478 , wherein the lipid nanoparticle comprises 40-50 mol % of the ionizable cationic lipid, 5-10 mol % of the neutral lipid, and 1-3 mol % of the polyethylene glycol (PEG)-modified lipid. 
     
     
         485 . A method of inducing an immune response in a subject, the method comprising administering to the subject the DENV mRNA vaccine of  claim 478  in an amount effective to produce an antigen-specific immune response in the subject.