Lipid nanoparticles for the prevention of tuberculosis or other mycobacterial infections

An immunogenic lipid nanoparticle (LNP) composition comprising:

• a mRNA polynucleotide sequence encoding one or more antigens encapsulated in a lipid nanoparticle comprising (a) one or more phospholipid(s) in a total amount of phospholipids of 5-20 mol % of the total lipid content of the LNP composition, the one or more phospholipid(s) comprising an anionic phospholipid selected from the group consisting of a phosphatidylserine (PS) or phosphatidylglycerol (PG) in a total amount of 2.5-10 mol % of the total lipid content of the LNP composition;
• (b) a sterol in a ratio of phospholipid to sterol of 0.25 to 0.42 and in a total amount of 0.5-50 mol % of the total lipid content of the LNP composition;
• (c) an ionizable cationic lipid at a N/P ratio of 3 to 8 relative to the mRNA polynucleotide in a total amount of 40-65 mol % of the total lipid content of the LNP composition;
• and (d) a PEG-conjugated lipid in a total amount of 0.5-2.5 mol % of the total lipid content of the LNP composition,
• wherein the ionizable cationic lipid comprises a 1,3-dioxolane ring that is (a) gem-disubstituted with a pair of hydrocarbon tails, and (b) further substituted with a dialkyl amino alkyl head group having a pKa of 6.2-7.5;
• the mRNA polynucleotide comprising one or more mRNA polynucleotide sequence(s) each encoding (i) a lysosome-associated membrane protein 1 (LAMP-1) signal peptide or a human HLA Class I signal peptide and (ii) a LAMP-1 or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to open reading frame(s) (ORF) of the mRNA polynucleotide.