Tropical disease vaccines

Abstract

The disclosure relates to tropical diseases such as viral mosquito borne illnesses and the treatment thereof. The invention includes ribonucleic acid vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines for treating and preventing tropical disease.

1 .- 185 . (canceled) 
     
     
         186 . A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding a Zika virus (ZIKV) polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 219 and an mRNA comprising an ORF encoding at least one Dengue virus (DENV) polypeptide. 
     
     
         187 . The composition of  claim 186 , wherein the ZIKV polypeptide comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 219. 
     
     
         188 . The composition of  claim 187 , wherein the ZIKV polypeptide comprises the amino acid sequence of SEQ ID NO: 219. 
     
     
         189 . The composition of  claim 186 , wherein the mRNA comprises a chemical modification. 
     
     
         190 . The composition of  claim 189 , wherein the chemical modification is 1-methylpseudouridine. 
     
     
         191 . The composition of  claim 190 , wherein the chemical modification is in the carbon-5 position of uracil. 
     
     
         192 . The composition of  claim 186 , wherein the RNA polynucleotide further comprises a 5′ terminal cap. 
     
     
         193 . The composition of  claim 192 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp. 
     
     
         194 . The composition of  claim 186 , wherein the composition further comprises a lipid nanoparticle. 
     
     
         195 . The composition of  claim 194 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a neutral lipid, a sterol, and polyethylene glycol (PEG)-modified lipid. 
     
     
         196 . The composition of  claim 195 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid. 
     
     
         197 . The composition of  claim 195 , wherein the ionizable cationic lipid is Compound 25, the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), the sterol is cholesterol, and the PEG-modified lipid is PEG-distearoyl glycerol (PEG-DMG). 
     
     
         198 . A composition comprising:
 an mRNA comprising an open reading frame encoding a ZIKV polypeptide comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 219, an mRNA comprising an ORF encoding at least one DENV polypeptide, and a lipid nanoparticle that comprises 40-50 mol % ionizable cationic lipid, 10-20 mol % neutral lipid, 35-45 mol % sterol, and 1-5 mol % PEG-modified lipid.   
     
     
         199 . The composition of  claim 198 , wherein the ZIKV polypeptide comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 219. 
     
     
         200 . The composition of  claim 199 , wherein the ZIKV polypeptide comprises the amino acid sequence of SEQ ID NO: 219. 
     
     
         201 . The composition of  claim 200 , wherein the ionizable cationic lipid is Compound 25, the neutral lipid is DSPC, the sterol is cholesterol, and the PEG-modified lipid is PEG-DMG. 
     
     
         202 . The composition of  claim 201 , wherein the mRNA comprises a chemical modification selected from 1-methylpseudouridine. 
     
     
         203 . The composition of  claim 202 , wherein the mRNA comprises a 7mG(5′)ppp(5′)NlmpNp 5′ terminal cap and a polyA tail. 
     
     
         204 . A method comprising administering to a subject the composition of  claim 186 . 
     
     
         205 . A method comprising administering to a subject the composition of  claim 203 .