MERS coronavirus vaccine
The present invention relates to mRNAs suitable for use as mRNA-based vaccines against infections with MERS coronaviruses. Additionally, the present invention relates to a composition comprising the mRNAs and the use of the mRNAs or the composition for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of MERS coronavirus infections. The present invention further describes a method of treatment or prophylaxis of infections with MERS coronavirus using the mRNA sequences.
1. A pharmaceutical composition comprising an isolated mRNA comprising at least one coding region, encoding a spike protein (S) of a Middle East respiratory (MERS) coronavirus, said coding region being at least 90% identical to a nucleic acid sequence of SEQ ID NO: 2361, wherein the mRNA is associated with lipid nanoparticles (LNPs).
2. The pharmaceutical composition according to claim 1 , wherein the mRNA further comprises at least one histone stem-loop.
3. The pharmaceutical composition according to claim 1 , wherein the mRNA comprises, in 5′ to 3′ direction, the following elements:
a) a 5′-cap structure,
b) the at least one coding region, and
c) a poly(A) sequence.
4. A method of treatment or prophylaxis of MERS coronavirus infections comprising the steps:
a) providing the pharmaceutical composition of claim 1 ; and
b) administering an effective amount of the pharmaceutical composition to an organism.
5. The method according to claim 4 , wherein the pharmaceutical composition is administered to the organism by subcutaneous, intramuscular or intradermal injection.
6. The method according to claim 5 , wherein the injection is carried out by using conventional needle injection or jet injection.
7. The pharmaceutical composition according to claim 3 , wherein the mRNA is associated with LNPs comprising: (i) a cationic lipid, (ii) an aggregation reducing agent, (iii) optionally, a non-cationic lipid, and (iv) optionally, a sterol.
8. The pharmaceutical composition according to claim 7 , wherein the aggregation reducing agent comprises a PEG-modified lipid.
9. The pharmaceutical composition according to claim 8 , wherein the mRNA is associated with LNPs comprising: (i) the cationic lipid, (ii) the PEG-modified lipid, (iii) the non-cationic lipid, and (iv) the sterol.
10. The pharmaceutical composition according to claim 9 , wherein the coding region of the mRNA is at least 95% identical to SEQ ID NO: 2361.
11. The pharmaceutical composition according to claim 9 , wherein the coding region of the mRNA is identical to SEQ ID NO: 2361.
12. The pharmaceutical composition according to claim 9 , wherein the mRNA further comprises a poly(A) sequence of 10 to 200 nucleotides.
13. The pharmaceutical composition according to claim 12 , wherein the mRNA further comprises a 5′ untranslated region (UTR) and/or a 3′ UTR.
14. The pharmaceutical composition according to claim 13 , wherein the mRNA further comprises a 5′ UTR and a 3′ UTR.