Vaccine compositions

A nucleic acid vaccine, comprising:

• one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent that causes an infectious disease, disorder, or condition,
• formulated within a lipid reconstructed natural messenger packs (LNMPs) comprising natural lipids and an ionizable lipid, wherein the ionizable lipid is selected from one of the following groups of compounds:
• i) a compound of formula
• a pharmaceutically acceptable salt thereof, or a stereoisomer of any of the foregoing, wherein:
• each A is independently C1-C16 branched or unbranched alkyl or C1-C16 branched or unbranched alkenyl, optionally substituted with heteroatom or substituted with OH, SH, or halogen;
• each B is independently C1-C16 branched or unbranched alkyl or C1-C16 branched or unbranched alkenyl, optionally substituted with heteroatom or substituted with OH, SH, or halogen;
• each X is independently a biodegradable moiety;
• and
• W is
• wherein:
• R5 is OH, SH, NR10R11;
• each R6 is independently H, C1-C3 branched or unbranched alkyl, C2-C3 branched or unbranched alkenyl, or cycloalkyl;
• each R7 and each R8 is independently H, C1-C3 branched or unbranched alkyl, C2-C3 branched or unbranched alkenyl, halogen, OH, SH, or NR10R11, wherein each R10 and R11 is independently H, C1-C3 alkyl, or R10 and Rn are taken together to form a heterocyclic ring;
• R7 and R8 are taken together to form a ring;
• each s is independently 1, 2, 3, 4, or 5;
• each u is independently 1, 2, 3, 4, or 5;
• t is 1, 2, 3, 4 or 5;
• each Z is independently absent, O, S, or NR12, wherein R12 is H, C1-C7 branched or unbranched alkyl, or C2-C7 branched or unbranched alkenyl, and
• Q is O, S, or NR13, wherein each R13 is H, or C1-C5 alkyl;
• ii) a compound of formula
• a pharmaceutically acceptable salt thereof, or a stereoisomer of any of the foregoing, wherein:
• is a cyclic or heterocyclic moiety;
• Y is alkyl, hydroxy, hydroxyalkyl or
• A is absent, —O—, —N(R7)—, —O-alkylene-, -alkylene-O—, —OC(O)—, —C(O)O—, —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(O)N(R7)—, —S—, —S—S—, or a bivalent heterocycle;
• each of X and Z is independently absent, —O—, —CO—, —N(R7)—, —O-alkylene-, -alkylene-O—, —OC(O)—, —C(O)O—, —N(R7)C(O)—, —C(O)N(R7)—, or —S—;
• each R7 is independently H, alkyl, alkenyl, cycloalkyl, hydroxy, hydroxyalkyl, or aminoalkyl;
• each M is independently a biodegradable moiety;
• each of R3, R40, R50, R60, R70, R80, R90, R100, R110, and R120 is independently H, C1-C16 branched or unbranched alkyl or C1-C16 branched or unbranched alkenyl, optionally interrupted with heteroatom or substituted with OH, SH, or halogen, or cycloalkyl or substituted cycloalkyl;
• each of l and m is an integer from 1 to 10;
• t1 is an integer from 0 to 10;
• and
• W is hydroxyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted amino, substituted or unsubstituted aminocarbonyl, or substituted or unsubstituted heterocyclyl or heteroaryl;
• and
• iii) a compound of formula
• pharmaceutically acceptable salts thereof, and stereoisomers of any of the foregoing, wherein:
• R20 and R30 are each independently H, C1-C5 branched or unbranched alkyl, or C2-C5 branched or unbranched alkenyl, or R20 and R30 together with the adjacent N atom form a 3 to 7 membered cyclic ring, optionally substituted with Ra;
• Ra is H, C1-C3 branched or unbranched alkyl, C2-C3 branched or unbranched alkenyl, halogen, OH, or SH;
• each R1 and each R2 is independently H, C1-C3 branched or unbranched alkyl, C2-C3 branched or unbranched alkenyl, OH, halogen, SH, or NR10R11, or
• R1 and R2 are taken together to form a cyclic ring;
• each R10 and R11 is independently H, C1-C3 branched or unbranched alkyl, C2-C3 branched or unbranched alkenyl, or R10 and R11 are taken together to form a heterocyclic ring;
• n is 0, 1, 2, 3 or 4;
• Y is O or S;
• Z is absent, O, S, or N(R12), wherein each R12 is independently H, C1-C7 branched or unbranched alkyl, or C2-C7 branched or unbranched alkenyl, provided that when Z is not absent, the adjacent R1 and R2 cannot be OH, NR10R11, or SH;
• v is 0, 1, 2, 3, or 4;
• y is 0, 1, 2, 3, or 4;
• each A is each independently C1-C16 branched or unbranched alkyl, or C2-C16 branched or unbranched alkenyl, optionally interrupted with one or more heteroatoms or optionally substituted with OH, SH, or halogen;
• each B is each independently C1-C16 branched or unbranched alkyl, or C2-C16 branched or unbranched alkenyl, optionally interrupted with one or more heteroatoms or optionally substituted with OH, SH, or halogen;
• and
• each X is independently a biodegradable moiety;
• and
• iv) a lipid comprising at least one head group and at least one tail group of formula (TI) or (TI′)
• a pharmaceutically acceptable salt thereof, or a stereoisomer of any of the foregoing,
• wherein:
• E is each independently —OC(O)—, —C(O)O—, —N(R7)C(O)—, —C(O)N(R7)—, —C(O—R13)—O—, —C(O)O(CH2)r—, —C(O)N(R7)(CH2)r—, —S—S—, or —C(O—R13)—O—(CH2)r—, wherein each R7 is independently H, alkyl, alkenyl, cycloalkyl, hydroxyalkyl, or aminoalkyl;
• R13 is branched or unbranched C3-C10 alkyl;
• r is 1, 2, 3, 4, or 5;
• Ra is each independently C1-C5 alkyl, C2-C5 alkenyl, or C2-C5 alkynyl;
• u1 and u2 are each independently 0, 1, 2, 3, 4, 5, 6, or 7;
• Rt is each independently H, C1-C16 branched or unbranched alkyl or C1-C16 branched or unbranched alkenyl, optionally interrupted with heteroatom or substituted with OH, SH, or halogen, or cycloalkyl or substituted cycloalkyl;
• represents the bond connecting the tail group to the head group;
• and
• wherein the lipid has a pKa from about 4 to about 8.