Zika virus mrna 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 . A Zika virus (ZIKV) composition, comprising:
 a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding at least one a ZIKV prME protein comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 97.   
     
     
         2 .- 28 . (canceled) 
     
     
         29 . The ZIKV composition of  claim 1 , wherein the prME protein is obtained from ZIKV strain MR 766, ZIKV strain ACD75819 or ZIKV strain SPH2015. 
     
     
         30 . The ZIKV composition of  claim 1 , wherein the RNA polynucleotide comprises at least one a chemical modification. 
     
     
         31 . The ZIKV composition of  claim 30 , 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. 
     
     
         32 . The ZIKV composition of  claim 30 , wherein the chemical modification is in the carbon 5-position of the uracil. 
     
     
         33 . The ZIKV composition of  claim 30 , wherein the chemical modification is a 1-methylpseudouridine. 
     
     
         34 . The ZIKV composition of  claim 30 , wherein at least 80% of the uracil in the open reading frame has a chemical modification. 
     
     
         35 . The ZIKV composition of  claim 34 , wherein 100% of the uracil in the open reading frame has a chemical modification. 
     
     
         36 . The ZIKV composition of  claim 1 , wherein the RNA polynucleotide further encodes a 5′ terminal cap. 
     
     
         37 . The ZIKV composition of  claim 36 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp. 
     
     
         38 .- 41 . (canceled) 
     
     
         42 . The ZIKV composition of  claim 1 , formulated in a lipid nanoparticle. 
     
     
         43 .- 44 . (canceled) 
     
     
         45 . The ZIKV composition of  claim 42 , wherein the lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. 
     
     
         46 . The ZIKV composition of  claim 45 , wherein the lipid nanoparticle carrier comprises a 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5%-25% non-cationic lipid. 
     
     
         47 . The ZIKV composition of  claim 45 , wherein the cationic lipid is an ionizable cationic lipid the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. 
     
     
         48 . The ZIKV composition of  claim 45 , wherein the cationic lipid is selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate. 
     
     
         49 .- 51 . (canceled) 
     
     
         52 . The ZIKV composition of  claim 1 , wherein the open reading frame is codon-optimized. 
     
     
         53 . (canceled) 
     
     
         54 . The ZIKV composition of  claim 1 , formulated in an effective amount to produce an antigen-specific immune response. 
     
     
         55 . A method of inducing an immune response in a subject, the method comprising administering to the subject the ZIKV composition of  claim 1 , in an amount effective to produce an antigen-specific immune response in the subject. 
     
     
         56 .- 477 . (canceled) 
     
     
         478 . The ZIKV composition of  claim 1 , wherein the prME protein has at least 95% identity to the amino acid sequence of SEQ ID NO: 97. 
     
     
         479 . The ZIKV composition of  claim 478 , wherein the prME protein comprises the amino acid sequence of SEQ ID NO: 97.