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 method comprising administering to a subject an immunogenic composition comprising a messenger ribonucleic acid (mRNA) that comprises an open reading frame (ORF) encoding a JEV signal peptide fused to a Zika virus (ZIKV) prME protein formulated in a lipid nanoparticle in an effective amount to induce in the subject a ZIKV prME-specific immune response, wherein the ORF comprises the sequence of SEQ ID NO: 1.
2. The method of claim 1 , wherein the effective amount reduces viral load in the subject by at least 80%, relative to a control, at 3-7 days following exposure to ZIKV, wherein the control is the viral load in a subject administered a ZIKV RNA vaccine lacking the JEV signal sequence.
3. The method of claim 1 , wherein the effective amount is sufficient to produce detectable levels of ZIKV prME protein as measured in serum of the subject at 1-72 hours post administration.
4. The method of claim 1 , wherein the effective amount is a total dose of 20 μg-200 μg.
5. The method of claim 1 , wherein the mRNA comprises the sequence of SEQ ID NO:20.
6. The method of claim 1 , wherein the immunogenic composition further comprises a 5′ untranslated region (UTR) comprising a sequence selected from SEQ ID NO:13 and SEQ ID NO:14.
7. The method of claim 1 , wherein the immunogenic composition further comprises a 3′ UTR comprising a sequence selected from SEQ ID NO:15 and SEQ ID NO:16.
8. The method of claim 1 , wherein the immunogenic composition comprises at least one modified nucleotide.
9. The method of claim 1 , wherein at least 80% of uracil nucleotides in the ORF have a chemical modification selected from N1-methyl-pseudouridine or N1-ethyl-pseudouridine.
10. The method of claim 1 , wherein the lipid nanoparticle comprises a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.
11. The method of claim 10 , wherein the ionizable cationic lipid comprises the following compound:
12. A method comprising administering to a subject an immunogenic composition comprising a messenger ribonucleic acid (mRNA) that comprises a 5′ UTR, an open reading frame (ORF) encoding a JEV signal peptide fused to a Zika virus (ZIKV) prME protein, and a 3′ UTR formulated in a lipid nanoparticle in an effective amount to induce in the subject a ZIKV prME-specific immune response, wherein the JEV signal peptide comprises the sequence of SEQ ID NO:18, the 5′ UTR comprises the sequence of SEQ ID NO:13, and the 3′UTR comprises the sequence of SEQ ID NO:15.
13. The method of claim 12 , wherein the effective amount reduces viral load in the subject by at least 80%, relative to a control, at 3-7 days following exposure to ZIKV, wherein the control is the viral load in a subject administered a ZIKV RNA vaccine lacking the JEV signal sequence.
14. The method of claim 12 , wherein the effective amount is sufficient to produce detectable levels of ZIKV prME protein as measured in serum of the subject at 1-72 hours post administration.
15. The method of claim 12 , wherein the effective amount is a total dose of 20 μg-200 μg.
16. The method of claim 12 , wherein the immunogenic composition comprises at least one modified nucleotide.
17. The method of claim 1 , wherein at least 80% of uracil nucleotides in the ORF have a chemical modification selected from N1-methyl-pseudouridine or N1-ethyl-pseudouridine.
18. The method of claim 12 , wherein the lipid nanoparticle comprises a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.
19. The method of claim 18 , wherein the ionizable cationic lipid comprises the following compound: