Bunyavirales vaccine
The present invention is directed to an artificial nucleic acid, particularly to an artificial RNA, and to polypeptides suitable for use in treatment or prophylaxis of an infection with a virus of the order Bunyavirales, particularly Severe fever with thrombocytopenia syndrome virus (SFTSV), Rift Valley fever virus (RVFV), or Crimean-Congo hemorrhagic fever virus (CCHFV), or a disorder related to such an infection. The present invention further concerns a Bunyavirales vaccine, particularly a SFTSV, RVFV, or CCHFV 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. A purified RNA comprising at least one coding sequence encoding at least one antigenic polypeptide derived a virus of the order Bunyavirales wherein the at least one antigenic polypeptide comprises a Nucleoprotein from Crimean-Congo hemorrhagic fever virus (CCHFV) that is at least 95% identical to SEQ ID NO: 589 and that is encoded by a sequence at least 90% identical to SEQ ID NOs: 6643, 7335 or 8027, wherein the RNA comprises a heterologous 5′UTR and/or 3′UTR element.
2. The purified RNA of claim 1 , wherein the at least one antigenic polypeptide comprises an amino acid sequence identical to SEQ ID NO: 589.
3. The purified RNA of claim 1 , wherein the at least one coding sequence comprises a IgE-leader sequence.
4. The purified RNA of claim 1 , wherein the RNA comprises 5′-cap structure.
5. The purified RNA of claim 4 , comprising:
a) the 5′-cap structure;
b) optionally, a 5′-UTR element;
c) the at least one coding sequence;
d) optionally, a 3′-UTR element;
e) optionally, a poly(C) sequence;
f) optionally a histone stem-loop; and
g) a poly(A) sequence of 10 to 200 adenosine.
6. A pharmaceutical composition comprising at least one purified RNA of claim 1 and at least one pharmaceutically acceptable carrier.
7. The pharmaceutical composition of claim 6 , wherein the at least one RNA is encapsulated in a lipid nanoparticle (LNP).
8. A method of treating or preventing a disease in a subject comprising administering an effective amount of a composition of claim 6 to the subject.
9. The method of claim 8 , wherein the composition is administered by injection.
10. The method of claim 9 , wherein the composition is administered by intramuscular or intradermal injection.
11. A kit comprising a composition of claim 6 and technical instructions providing information on administration of said composition.
12. The purified RNA of claim 1 , wherein the at least one coding sequence encoding at least one antigenic polypeptide is at least about 90% identical to SEQ ID NO: 8027.
13. The purified RNA of claim 1 , wherein the at least one coding sequence encoding at least one antigenic polypeptide is at least about 90% identical to SEQ ID NO: 6643.
14. The purified RNA of claim 1 , wherein the at least one coding sequence encoding at least one antigenic polypeptide is at least about 90% identical to SEQ ID NO: 7335.
15. The purified RNA of claim 1 , wherein the RNA comprises a modified nucleotide.
16. The purified RNA of claim 15 , wherein the modified nucleotide is pseudouridine or 1-methyl-pseudouridine.
17. The pharmaceutical composition of claim 6 , wherein the composition comprises at least one further purified RNA encoding a CCHFV antigen.
18. The pharmaceutical composition of claim 17 , wherein the at least one further purified RNA encodes a CCHFV glycoprotein.
19. The pharmaceutical composition of claim 18 , wherein the CCHFV glycoprotein is a Gc protein at least 95% identical to the sequence of SEQ ID NO: 1665.
20. The pharmaceutical composition of claim 19 , wherein the Gc protein is encoded by a sequence at least 90% identical to SEQ ID NOs: 12,389, 14,032 or 15,675.