Combination HMPV/RSV RNA vaccines
The disclosure relates to respiratory virus ribonucleic acid (RNA) vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.
1. A messenger ribonucleic acid (mRNA) vaccine, comprising:
(a) an mRNA comprising an open reading frame encoding a human metapneumovirus (hMPV) F protein;
(b) an mRNA comprising an open reading frame encoding a respiratory syncytial virus (RSV) F protein; and
(c) a lipid nanoparticle comprising 20-60 mol % cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid.
2. The mRNA vaccine of claim 1 , wherein the mRNA of (a) is chemically modified, and the mRNA of (b) is chemically modified.
3. The mRNA vaccine of claim 2 , wherein 100% of the uracil in the open reading frame of the mRNA of (a) comprises a 1-methylpseudouridine, and 100% of the uracil in the open reading frame of the mRNA of (b) comprises a 1-methylpseudouridine.
4. The mRNA vaccine of claim 3 , wherein the 1-methylpseudouridine is in the carbon 5 position of the uracil.
5. The mRNA vaccine of claim 1 , wherein the cationic lipid is an ionizable cationic lipid, the neutral lipid is distearoylphosphatidylcholine (DSPC), and the sterol is cholesterol.
6. The mRNA vaccine of claim 5 , wherein the ionizable cationic lipid is Compound 25:
7. The mRNA vaccine of claim 5 , wherein the ionizable cationic lipid is a compound of Formula (I):
and wherein
R 1 is R″M′R′ or C 5-20 alkenyl;
R 2 and R 3 are each independently selected from C 1-14 alkyl and C 2-14 alkenyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is selected from 3, 4, and 5;
M and M′ are each independently —OC(O)— or —C(O)O—;
R 5 , R 6 , and R 7 are each H;
R′ is a linear C 1-12 alkyl, or C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl;
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
8. The mRNA vaccine of claim 7 , wherein:
R 1 is R″M′R′;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 4;
M and M′ are each independently —OC(O)—;
R 5 , R 6 , and R 7 are each H;
R′ is C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl; and
m is 6.
9. The mRNA vaccine of claim 7 , wherein:
R 1 is C 5-20 alkenyl;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 3;
M is —C(O)O—;
R 5 , R 6 , and R 7 are each H; and
m is 6.
10. A messenger ribonucleic acid (mRNA) vaccine, comprising:
(a) an mRNA comprising an open reading frame encoding a human metapneumovirus (hMPV) F protein;
(b) an mRNA comprising an open reading frame encoding a respiratory syncytial virus (RSV) F protein; and
(c) a lipid nanoparticle comprising 20-60 mol % ionizable cationic lipid, 5-25 mol % distearoylphosphatidylcholine (DSPC), 25-55 mol % cholesterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid,
wherein 100% of the uracil in the open reading frame of the mRNA of (a) comprises a 1-methylpseudouridine, and 100% of the uracil in the open reading frame of the mRNA of (b) comprises a 1-methylpseudouridine.
11. The mRNA vaccine of claim 10 , wherein the ionizable cationic lipid is Compound 25:
12. The mRNA vaccine of claim 10 , wherein the ionizable cationic lipid is a compound of Formula (I):
and wherein
R 1 is R″M′R′ or C 5-20 alkenyl;
R 2 and R 3 are each independently selected from C 1-14 alkyl and C 2-14 alkenyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is selected from 3, 4, and 5;
M and M′ are each independently —OC(O)— or —C(O)O—;
R 5 , R 6 , and R 7 are each H;
R′ is a linear C 1-12 alkyl, or C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl;
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
13. The mRNA vaccine of claim 12 , wherein:
R 1 is R″M′R′;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 4;
M and M′ are each independently —OC(O)—;
R 5 , R 6 , and R 7 are each H;
R′ is C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl; and
m is 6.
14. The mRNA vaccine of claim 12 , wherein:
R 1 is C 5-20 alkenyl;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 3;
M is —C(O)O—;
R 5 , R 6 , and R 7 are each H; and
m is 6.