| abstract |
A composition comprising at least one mRNA comprising at least one coding sequence coding for a SARS-CoV-2 spike protein (S) according to SEQ ID NO: 10 or variants thereof with at least 95% sequence identity, wherein the mRNA at least one heterologous comprises untranslated region (UTR),wherein the encoded spike protein (S) is a prefusion-stabilized spike protein (S_stab) having at least one prefusion-stabilizing mutation, the at least one prefusion-stabilizing mutation comprising the following amino acid substitutions: K986P and V987P,wherein the A composition comprising at least one pharmaceutically acceptable carrier, and wherein the at least one mRNA is complexed with one or more lipid(s) to form lipid nanoparticles (LNP), the LNP comprising:(i) a lipid of formula (III- 3) as at least one cationic lipid; (ii) 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) as at least one neutral lipid; (iii ) cholesterol as at least one steroid or steroid analogue; and(iv) a PEG-lipid of formula (IVa) as at least one polymer-conjugated lipidwherein "n" corresponds to an average value in a range from 30 to 60, with (i) to (iv) in a molar ratio of about 20-60 % cationic lipid, 5-25% neutral lipid, 25-55% sterol and 0.5-15% PEG lipid. |