Zika virus vaccine
The present invention is directed to an artificial nucleic acid and to polypeptides suitable for use in treatment or prophylaxis of an infection with Zika virus or a disorder related to such an infection. In particular, the present invention concerns a Zika virus vaccine. The present invention is directed to an artificial nucleic acid, polypeptides, compositions and vaccines comprising the artificial nucleic acid or the polypeptides. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the artificial nucleic acid, polypeptides, compositions and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the artificial nucleic acid, polypeptides, compositions and vaccines.
1. An artificial nucleic acid comprising at least one coding region encoding at least one polypeptide comprising Zika virus envelope protein (E), wherein the artificial nucleic acid is a mRNA comprising, in 5′ to 3′ direction, the following elements:
a) a 5′-CAP structure,
b) the at least one coding region comprising a modified nucleic acid sequence encoding the at least one polypeptide comprising Zika virus envelope protein (E), wherein the at least one polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 552, wherein the at least one coding region comprises a nucleic acid sequence identical to the polypeptide coding region of SEQ ID NO: 5520 or a sequence at least 95% identical to the polypeptide coding region of SEQ ID NO: 5520,
c) a heterologous 3′-UTR element comprising a nucleic acid sequence, and
d) a poly(A) sequence comprising 10 to 200 adenosine nucleotides.
2. The artificial nucleic acid according to claim 1 , further comprising
at least one heterologous 5′ untranslated region (UTR) element.
3. The artificial nucleic acid according to claim 1 , wherein the artificial nucleic acid comprises at least one histone stem-loop.
4. The artificial nucleic acid according to claim 1 , wherein the at least one encoded polypeptide comprises at least one signal sequence.
5. The artificial nucleic acid according to claim 1 , wherein the G/C content of the at least one coding region is increased compared to the G/C content of a reference RNA encoding the at least one polypeptide.
6. The artificial nucleic acid according to claim 1 , wherein the at least one heterologous 3′-UTR element comprises a nucleic acid sequence derived from a 3′-UTR of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen alpha gene.
7. The artificial nucleic acid according to claim 2 , wherein the at least one heterologous 5′-UTR element comprises a nucleic acid sequence, which is derived from the 5′-UTR of a TOP gene.
8. A composition comprising at least one artificial nucleic acid as defined by claim 1 and a pharmaceutically acceptable carrier.
9. The composition according to claim 8 , wherein the at least one artificial nucleic acid is complexed at least partially with a cationic or polycationic compound and/or a polymeric carrier.
10. A kit or kit of parts comprising the artificial nucleic acid according to claim 1 , optionally a liquid vehicle for solubilising, and optionally technical instructions providing information on administration and dosage of the components.
11. A method of treating a subject with, or protecting a subject from, an infection with Zika virus or a disorder related to an infection with Zika virus comprising administering to said subject the artificial nucleic acid according to claim 1 .
12. The artificial nucleic acid according to claim 1 , wherein the at least one polypeptide comprises a stem region of the Japanese encephalitis virus E protein.
13. The artificial nucleic acid according to claim 1 , wherein the modified nucleic acid sequence comprises a nucleotide with a base modification selected from pseudouridine or 1-methyl-pseudouridine.
14. The artificial nucleic acid according to claim 1 , wherein the at least one polypeptide comprises the amino acid sequence according to SEQ ID NO: 552.
15. The artificial nucleic acid according to claim 14 , wherein the coding region comprises a modified nucleic acid sequence that comprises a nucleotide with a base modification selected from pseudouridine or 1-methyl-pseudouridine.