Zika RNA vaccines
Aspects of the disclosure describe compositions that comprise RNA polynucleotides having an open reading frame encoding one or more Zika virus antigens. Methods for preparing and using the compositions are also described.
1. A Zika virus (ZIKV) immunogenic composition, comprising:
a messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame encoding a ZIKV antigenic polypeptide formulated in a lipid nanoparticle.
2. The ZIKV immunogenic composition of claim 1 , wherein the antigenic polypeptide is a ZIKV polyprotein.
3. The ZIKV immunogenic composition of claim 1 , wherein the antigenic polypeptide is selected from the group consisting of a ZIKV capsid protein, a ZIKV premembrane/membrane protein, a ZIKV envelope protein, a ZIKV non-structural protein 1, a ZIKV non-structural protein 2A, a ZIKV non-structural protein 2B, a ZIKV non-structural protein 3, a ZIKV non-structural protein 4A, a ZIKV non-structural protein 4B, and a ZIKV non-structural protein 5.
4. The ZIKV immunogenic composition of claim 3 , wherein the antigenic polypeptide comprises a ZIKV capsid protein, a ZIKV premembrane/membrane protein, and a ZIKV envelope protein.
5. The ZIKV immunogenic composition of claim 3 , wherein the antigenic polypeptide comprises a ZIKV capsid protein and a ZIKV premembrane/membrane protein.
6. The ZIKV immunogenic composition of claim 3 , wherein the antigenic polypeptide comprises a ZIKV capsid protein and a ZIKV envelope protein.
7. The ZIKV immunogenic composition of claim 3 , wherein the antigenic polypeptide comprises a ZIKV premembrane/membrane protein and a ZIKV envelope protein.
8. The ZIKV immunogenic composition of claim 1 , wherein the open reading frame encodes at least two ZIKV antigenic polypeptides.
9. The ZIKV immunogenic composition of claim 1 , wherein the immunogenic composition comprises at least two RNA polynucleotides each having an open reading frame encoding a ZIKV antigenic polypeptide.
10. The ZIKV immunogenic composition of claim 1 , wherein the antigenic polypeptide is obtained from ZIKV strain MR 766, ZIKV strain ACD75819 or ZIKV strain SPH2015.
11. The ZIKV immunogenic composition of claim 1 , wherein the RNA polynucleotide comprises a chemical modification.
12. The ZIKV immunogenic composition of claim 11 , wherein the chemical modification is a N1-methylpseudouridine.
13. The ZIKV immunogenic composition of claim 11 , wherein at least 80% of the uracil in the open reading frame have a chemical modification.
14. The ZIKV immunogenic composition of claim 13 , wherein 100% of the uracil in the open reading frame has a chemical modification.
15. The ZIKV immunogenic composition of claim 1 , wherein the RNA polynucleotide further encodes a 5′ terminal cap.
16. The ZIKV immunogenic composition of claim 15 , wherein the 5′ terminal cap is 7 mG(5′)ppp(5′)NlmpNp.
17. The ZIKV immunogenic composition of claim 1 , wherein the lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid.
18. The ZIKV immunogenic composition of claim 17 , wherein the lipid nanoparticle comprises a molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid.
19. The ZIKV immunogenic composition of claim 17 , wherein the cationic lipid is an ionizable cationic lipid, the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
20. The ZIKV immunogenic composition of claim 17 , wherein the cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
21. A method of inducing an immune response in a subject, the method comprising administering to the subject a ZIKV immunogenic composition comprising a messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame encoding a ZIKV antigenic polypeptide, in an amount effective to produce an antigen-specific immune response in the subject.
22. A Zika virus (ZIKV) immunogenic composition, comprising a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding a ZIKV antigenic polypeptide, a 5′ terminal cap, and a chemical modification, wherein the immunogenic composition is formulated within a lipid nanoparticle.
23. The ZIKV immunogenic composition of claim 22 , wherein at least 80% of the uracil in the open reading frame have a chemical modification.
24. A Zika virus (ZIKV) immunogenic composition, comprising a messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame encoding a ZIKV polypeptide linked to a signal peptide.
25. The ZIKV immunogenic composition of claim 24 , wherein the ZIKV antigenic polypeptide is a ZIKV PrM protein, a ZIKV envelope (E) protein, or a ZIKV prME fusion protein.
26. The ZIKV immunogenic composition of claim 24 , wherein the ZIKV antigenic polypeptide is fused to a signal peptide selected from the group consisting of: a HuIgGk signal peptide (METPAQLLFLLLLWLPDTTG; SEQ ID NO: 125); IgE heavy chain epsilon-1signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO: 126); Japanese encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 128) and VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 131).
27. The immunogenic composition of claim 1 , further comprising a RNA polynucleotide having an open reading frame encoding a CHIKV antigenic polypeptide and/or a DENV antigenic polypeptide.