Zika virus mRNA vaccines
Provided herein, in some embodiments, are Zika virus RNA vaccines and methods of producing an antigen-specific immune response in a subject.
1. A composition comprising a messenger ribonucleic acid (mRNA) comprising a 5′ untranslated region (UTR), an open reading frame (ORF) encoding a JEV signal peptide fused to a Zika virus (ZIKV) prME protein, and a 3′ UTR, wherein the mRNA is formulated in a lipid nanoparticle, and the ORF comprises a nucleotide sequence having at least 98% identity to the nucleotide sequence of SEQ ID NO: 1.
2. The composition of claim 1 , wherein the ORF comprises the nucleotide sequence of SEQ ID NO: 1.
3. The composition of claim 1 , wherein the ZIKV prME protein comprises the amino acid sequence of SEQ ID NO: 7.
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-methyl-pseudouridine.
6. The composition of claim 1 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a non-cationic lipid, a sterol, and a PEG-modified lipid.
7. The composition of claim 6 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % non-cationic lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid.
8. The composition of claim 6 , wherein the ionizable cationic lipid comprises the following compound:
9. A method comprising administering to a subject the composition of claim 1 in an effective amount to induce in the subject a ZIKV-specific immune response.
10. A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding a Zika virus (ZIKV) prME protein, wherein the mRNA is formulated in a lipid nanoparticle, and the ORF comprises the nucleotide sequence of SEQ ID NO: 1.
11. The composition of claim 10 , wherein the ZIKV prME protein comprises the amino acid sequence of SEQ ID NO: 7.
12. The composition of claim 10 , wherein the mRNA further comprises a 5′ UTR that comprises a sequence selected from SEQ ID NO: 13 and SEQ ID NO: 14.
13. The composition of claim 10 , wherein the mRNA further comprises a 3′ UTR that comprises a sequence selected from SEQ ID NO: 15 and SEQ ID NO: 16.
14. The composition of claim 10 , wherein the mRNA comprises a chemical modification.
15. The composition of claim 14 , wherein the chemical modification is 1-methyl-pseudouridine.
16. The composition of claim 10 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a non-cationic lipid, a sterol, and a PEG-modified lipid.
17. The composition of claim 16 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % non-cationic lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid.
18. The composition of claim 17 , wherein the ionizable cationic lipid comprises the following compound:
19. A method comprising administering to a subject the composition of claim 10 in an effective amount to induce in the subject a ZIKV prME-specific immune response.
20. The composition of claim 10 , wherein the mRNA further comprises a 5′ UTR that comprises the sequence of SEQ ID NO: 13 and a 3′ UTR that comprises the sequence of SEQ ID NO: 15.
21. The composition of claim 10 , wherein the mRNA further comprises a 5′ UTR that comprises the sequence of SEQ ID NO: 14 and a 3′ UTR that comprises the sequence of SEQ ID NO: 16.
22. The composition of claim 1 , wherein the 5′ UTR comprises a sequence selected from SEQ ID NO: 13 and SEQ ID NO: 14.
23. The composition of claim 1 , wherein the 3′ UTR comprises a sequence selected from SEQ ID NO: 15 and SEQ ID NO: 16.
24. The composition of claim 1 , wherein the 5′ UTR comprises the sequence of SEQ ID NO: 13 and the 3′ UTR comprises the sequence of SEQ ID NO: 15.
25. The composition of claim 1 , wherein the 5′ UTR comprises the sequence of SEQ ID NO: 14 and the 3′ UTR comprises the sequence of SEQ ID NO: 16.