Zika virus RNA vaccines
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. A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a Zika virus (ZIKV) polypeptide that (a) comprises the amino acid sequence of SEQ ID NO: 427 and (b) has at least 90% identity to the amino acid sequence of SEQ ID NO: 219.
2. The composition of claim 1 , wherein the ZIKV polypeptide comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 219.
3. The composition of claim 2 , wherein the ZIKV polypeptide comprises the amino acid sequence of SEQ ID NO: 219.
4. The composition of claim 1 , wherein the mRNA comprises a chemical modification.
5. The composition of claim 4 , wherein the chemical modification is 1-methylpseudouridine or 1-ethylpseudouridine.
6. The composition of claim 4 , wherein the chemical modification is in the carbon-5 position of uracil.
7. The composition of claim 1 , wherein the RNA polynucleotide further comprises a 5′ terminal cap.
8. The composition of claim 7 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)N1mpNp.
9. The composition of claim 1 , wherein the composition further comprises a lipid nanoparticle.
10. The composition of claim 9 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a neutral lipid, a sterol, and polyethylene glycol (PEG)-modified lipid.
11. The composition of claim 10 , 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.
12. The composition of claim 10 , 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).
13. A composition comprising:
an mRNA comprising an open reading frame encoding a ZIKV polypeptide that (a) comprises the amino acid sequence of SEQ ID NO: 427 and (b) has at least 95% identity to the amino acid sequence of SEQ ID NO: 219 and a lipid nanoparticle that comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid.
14. The composition of claim 13 , wherein the ZIKV polypeptide comprises the amino acid sequence of SEQ ID NO: 219.
15. The composition of claim 14 , 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.
16. The composition of claim 15 , wherein the mRNA comprises a chemical modification selected from 1-methylpseudouridine or 1-ethylpseudouridine.
17. The composition of claim 16 , wherein the chemical modification is in the carbon-5 position of uracil.
18. The composition of claim 17 , wherein the mRNA comprises a 7mG(5′)ppp(5′)N1mpNp 5′ terminal cap and a polyA tail.
19. A method comprising administering to a subject the composition of claim 1 .
20. A method comprising administering to a subject the composition of claim 18 .