Zika virus RNA vaccines
View Patent ↗The disclosure relates to Zika virus infection and the treatment thereof. The invention includes ribonucleic acid compositions, as well as methods of using the compositions for treating and preventing Zika virus infection.
1. An immunogenic composition comprising a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding an antigenic Zika virus (ZIKV) prME protein that comprises the amino acid sequence of SEQ ID NO: 203, wherein the RNA polynucleotide is formulated in a lipid nanoparticle that 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, in an effective amount to induce an immune response in a subject.
2. The immunogenic composition of claim 1 , wherein the RNA polynucleotide further encodes at a 5′ terminal cap, 7mG(5′)ppp(5′)N1mpNp.
3. The immunogenic composition of claim 1 , wherein at least 80% of the uracil in the open reading frame has a chemical modification selected from N1-methyl-pseudouridine and N1-ethyl-pseudouridine.
4. The immunogenic composition of claim 3 , wherein the chemical modification is in the carbon 5-position of the uracil.
5. The immunogenic composition of claim 1 , wherein the efficacy of the composition is at least 60%, relative to unvaccinated subjects, following a single dose of the composition.
6. The immunogenic composition of claim 5 , wherein the efficacy of the composition is at least 70%, relative to unvaccinated subjects, following a single dose of the composition.
7. The immunogenic composition of claim 6 , wherein the efficacy of the composition is at least 80%, relative to unvaccinated subjects, following a single dose of the composition.
8. The immunogenic composition of claim 7 , wherein the efficacy of the composition is at least 90%, relative to unvaccinated subjects, following a single dose of the composition.
9. The immunogenic composition 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.
10. The immunogenic composition of claim 1 , wherein the effective amount is sufficient to produce a 1,000-10,000 neutralization titer produced by neutralizing antibody against the ZIKV prME protein as measured in serum of the subject at 1-72hours post administration.
11. The immunogenic composition of claim 1 , wherein an anti-ZIKV prME protein antibody titer produced in the subject is increased by at least 1 log relative to a control, wherein the control is an anti-ZIKV prME protein antibody titer produced in a subject who has not been administered any vaccine against ZIKV.
12. The immunogenic composition of claim 1 , wherein the anti-ZIKV prME protein antibody titer produced in the subject is increased at least 2 times relative to a control, wherein the control is an anti-ZIKV prME protein antibody titer produced in a subject who has not been administered any vaccine against ZIKV.
13. The immunogenic composition of claim 1 , wherein the effective amount is a total dose of 25 μg-200 μg.
14. The immunogenic composition of claim 13 , wherein the effective amount is a total dose of 25 μg-100 μg.
15. The immunogenic composition of claim 1 , wherein the ionizable cationic lipid comprises the following compound:
16. The immunogenic composition of claim 1 , wherein the RNA polynucleotide has an open reading frame that comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 139.
17. The immunogenic composition claim 16 , wherein the RNA polynucleotide has an open reading frame that comprises the nucleotide sequence of SEQ ID NO: 139.
18. The immunogenic composition of claim 1 , wherein the ZIKV composition further comprises a RNA polynucleotide having an open reading frame encoding antigenic Chikungunya virus (CHIKV) polyprotein comprising E1 protein and/or E2 protein.
19. The immunogenic composition of claim 18 , wherein the antigenic CHIKV polyprotein further comprises C protein, E1 protein, E2 protein and E3 protein.
20. The immunogenic composition of claim 19 , wherein the antigenic CHIKV polyprotein comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 408.
21. The immunogenic composition of claim 19 , wherein the RNA polynucleotide having an open reading frame encoding antigenic CHIKV polyprotein comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 401.
22. The immunogenic composition of claim 1 , wherein the ZIKV composition further comprises a RNA polynucleotide having an open reading frame encoding antigenic Dengue virus (DENV) polypeptide.
23. The immunogenic composition of claim 22 , wherein the antigenic DENV polypeptide comprises an antigenic DENV prME protein.
24. The immunogenic composition of claim 23 , wherein the antigenic DENV prME protein comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 267.
25. The immunogenic composition of claim 23 , wherein the RNA polynucleotide having an open reading frame encoding antigenic DENV prME protein comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 248.
26. An immunogenic composition comprising a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding an antigenic ZIKV prME protein that comprises the amino acid sequence of SEQ ID NO: 203.