Respiratory syncytial virus vaccine

A vaccine, comprising:

• at least one ribonucleic acid (RNA) polynucleotide having an open reading frame encoding at least one respiratory syncytial virus (RSV) antigenic polypeptide, at least one 5′ terminal cap, and optionally at least one chemical modification, formulated within a lipid nanoparticle comprising a cationic lipid selected from compounds of Formula (I):
• or a salt or isomer thereof, wherein:
• R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
• R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
• R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR, —CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —N(R)2, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;
• each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
• R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
• R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
• each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
• each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
• each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
• each Y is independently a C3-6 carbocycle;
• each X is independently selected from the group consisting of F, Cl, Br, and I;
• and
• m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.

A vaccine, comprising:

• at least one ribonucleic acid (RNA) polynucleotide having an open reading frame encoding membrane-bound respiratory syncytial virus (RSV) F protein, membrane-bound DS-Cav1 (stabilized prefusion RSV F protein), or a combination of membrane-bound RSV F protein and membrane-bound DS-Cav1 formulated in a lipid nanoparticle comprising a cationic lipid selected from compounds of Formula (I):
• or a salt or isomer thereof, wherein:
• R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
• R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
• R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR, —CQ(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)—N(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —N(R)2, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(R)R8, —O(CH2)n—OR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;
• each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
• R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
• R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
• each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
• each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
• each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
• each Y is independently a C3-6 carbocycle;
• each X is independently selected from the group consisting of F, Cl, Br, and I;
• and
• m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.