Lassa virus vaccine
The present invention provides mRNAs usable as vaccines against lassa virus (LASV) infections. Further, the invention relates to (pharmaceutical) compositions and vaccines comprising said mRNAs and their use for treatment or prophylaxis of a lassa virus infection. The present invention further features a kit comprising the mRNAs, (pharmaceutical) compositions or vaccines and a method for treatment or prophylaxis of lassa virus infections using said mRNAs, pharmaceutical) compositions or vaccines.
1. An mRNA comprising at least one coding region, said coding region encoding a glycoprotein precursor (GPC) of a lassa virus, said coding region comprising a RNA sequence at least about 95% identical to one of SEQ ID NOs: 751-936, 1126-1311, 1501-1686, 1876-2061, 2251-2436,2626-2811 or 3001-3186, wherein said mRNA comprises a 5′ cap, a heterologous 3′-UTR element and Poly-A sequence.
2. The mRNA of claim 1 , wherein the lassa virus is from lassa virus clade I.
3. The mRNA of claim 1 , wherein the mRNA is a modified mRNA.
4. The mRNA of claim 1 , wherein the coding region comprises an RNA sequence as defined by any one of SEQ ID NOs: 751-936, 1126-1311, 1501-1686, 1876-2061, 2251-2436, 2626-2811 or 3001-3186.
5. The mRNA of claim 1 , wherein the G/C content of the coding region of the mRNA is increased compared to the G/C content of the corresponding coding sequence of the wild type mRNA, or wherein the C content of the coding region of the mRNA is increased compared to the C content of the corresponding coding sequence of the wild type mRNA, or wherein the codon usage in the coding region of the mRNA is adapted to the human codon usage, or wherein the codon adaptation index (CAI) is increased or maximised in the coding region of the mRNA, wherein the encoded amino acid sequence of the mRNA is not modified compared to the encoded amino acid sequence of an original mRNA encoding the amino acid sequence.
6. The mRNA of claim 1 , wherein the mRNA comprises at least one histone stem-loop.
7. The mRNA of claim 6 , wherein the at least one histone stem loop comprises a nucleic acid sequence according to SEQ ID NO: 3394.
8. The mRNA of claim 1 , wherein the poly(A) sequence comprises 10 to 200 adenosine nucleotides.
9. The mRNA of claim 1 , wherein the 3′-UTR element comprises a nucleic acid sequence derived from a 3′-UTR of an alpha-globin gene.
10. The mRNA of claim 1 , wherein the mRNA sequence comprises a 5′-UTR element.
11. The mRNA of claim 10 , wherein the 5′-UTR element comprises or consists of a nucleic acid sequence which is derived from a 5′-UTR of a TOP gene encoding a ribosomal protein.
12. A composition comprising at least one mRNA of claim 1 and a pharmaceutically acceptable carrier.
13. The composition of claim 12 , wherein the at least one mRNA is complexed with one or more cationic or polycationic compounds.
14. The composition of claim 12 , wherein the mRNA is complexed or associated with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.
15. The composition of claim 12 , wherein the composition comprises at least one adjuvant.
16. A method of treatment or prophylaxis of lassa infections comprising the steps: 13:
a) providing a composition according to claim 13 ; and
b) administering the composition to an organism.
17. The method of claim 16 , wherein the administering the composition is by injection of the composition.
18. The method of claim 17 , wherein the injection is an intramuscular injection.