Chikungunya 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 Chikungunya virus (CHIKV) polypeptide and a lipid nanoparticle, wherein the lipid nanoparticle comprises an ionizable cationic lipid of Compound 25:
2. The composition of claim 1 , wherein the CHIKV polypeptide is selected from the group consisting of CHIKV E1 proteins, CHIKV E2 proteins, CHIKV E3 proteins, CHIKV 6K proteins, and CHIKV capsid (C) proteins.
3. The composition of claim 2 , wherein the CHIKV polypeptide comprises a CHIKV E1 protein.
4. The composition of claim 2 , wherein the CHIKV polypeptide comprises a CHIKV E2 protein.
5. The composition of claim 2 , wherein the CHIKV polypeptide is a polyprotein comprising a CHIKV C protein, a CHIKV E3 protein, a CHIKV E2 protein, a CHIKV 6K protein, and a CHIKV E1 protein.
6. The composition of claim 5 , wherein the CHIKV polyprotein comprises an amino acid sequence having at least 90% identity to the sequence of SEQ ID NO: 413.
7. The composition of claim 6 , wherein the CHIKV polyprotein comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 413.
8. The composition of claim 7 , wherein the CHIKV polyprotein comprises the amino acid sequence of SEQ ID NO: 413.
9. The composition of claim 1 , wherein the open reading frame comprises a nucleic acid sequence having at least 80% identity to the open reading frame sequence of SEQ ID NO: 401.
10. The composition of claim 9 , wherein the open reading frame comprises a nucleic acid sequence having at least 90% identity to the open reading frame sequence of SEQ ID NO: 401.
11. The composition of claim 1 , wherein the mRNA comprises a chemical modification.
12. The composition of claim 11 , wherein the chemical modification is 1-methylpseudouridine or 1-ethylpseudouridine.
13. The composition of claim 11 , wherein the chemical modification is in the carbon-5 position of uracil.
14. The composition of claim 1 , wherein the mRNA further comprises a 5′ terminal cap.
15. The composition of claim 14 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp.
16. The composition of claim 1 , wherein the lipid nanoparticle further comprises a neutral lipid, a sterol, and a polyethylene glycol (PEG)-modified lipid.
17. The composition of claim 16 , 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.
18. The composition of claim 16 , wherein 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).
19. The composition of claim 1 further comprising an adjuvant.
20. A method comprising administering to a subject the composition of claim 1 .