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 method of treatment or prophylaxis of Middle East respiratory syndrome (MERS) coronavirus infections comprising the steps:
a) providing a composition comprising a mRNA comprising at least one coding region, encoding an antigenic protein comprising a spike protein (S) of a Middle East respiratory (MERS) coronavirus, said coding sequence being at least 90% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2373, 2374, 2375, 2376, 2377 and 2378, wherein the mRNA is associated with lipid nanoparticles (LNPs); and
b) administering an effective amount of the composition to an organism, thereby stimulating a humoral immune response to the antigenic protein in the organism.
2. The method of claim 1 , wherein the mRNA is associated with LNPs comprising: (i) a cationic lipid, (ii) a PEG-modified lipid, (iii) a non-cationic lipid and (iv) a sterol.
3. The method according to claim 1 , wherein the mRNA is administered to the organism by subcutaneous, intramuscular or intradermal injection.
4. The method according to claim 3 , wherein the injection is carried out by using conventional needle injection or jet injection.
5. The method of claim 1 , 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.
6. The method of claim 5 , wherein the aggregation reducing agent comprises a PEG-modified lipid.
7. The method of claim 6 , 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.
8. The method of claim 1 , wherein said coding region encodes a stabilized spike protein (S_stabilized) of a MERS coronavirus having the amino acid residue at position 1060 changed to Proline and the amino acid residue at position 1061 changed to Proline, said coding region being at least 90% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2373, 2374, 2375, 2376, 2377 and 2378.
9. The method of claim 1 , wherein the mRNA comprises at least one histone stem-loop.
10. The method of claim 1 , wherein the mRNA comprises, in 5′ to 3′ direction, the following elements:
a) a 5′-cap structure,
b) said at least one coding region,
c) a poly(A) tail,
d) optionally a poly(C) tail, and
e) optionally a histone stem-loop.