Zoonotic disease RNA vaccines
Provide herein are Lassa virus, Nipah virus, and betacoronavirus ribonucleic acid vaccines as well as methods of using the vaccines and compositions comprising the vaccines.
1. A composition comprising:
(a) a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding a fusion protein, wherein the fusion protein comprises a Nipah virus F protein and a Nipah virus G protein; and
(b) a lipid nanoparticle,
wherein the lipid nanoparticle comprises 45-55 mol % ionizable lipid, 5-25 mol % neutral lipid, 35-45 mol % sterol, and 0.5-5 mol % polyethylene glycol (PEG)-modified lipid,
wherein the ionizable 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.
2. The composition of claim 1 , 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.
3. The composition of claim 1 , 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.
4. The composition of claim 1 , wherein the compound is:
5. The composition of claim 1 , wherein the sterol is cholesterol.
6. The composition of claim 1 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
7. The composition of claim 1 , wherein the PEG-modified lipid is PEG-DMG.
8. The composition of claim 1 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.
9. The composition of claim 2 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.
10. The composition of claim 3 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.
11. The composition of claim 4 , wherein the sterol is cholesterol, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.
12. The composition of claim 1 , wherein the ORF comprises chemically-modified uracil residues.
13. The composition of claim 12 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine.
14. The composition of claim 2 , wherein the ORF comprises chemically-modified uracil residues.
15. The composition of claim 14 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine.
16. The composition of claim 3 , wherein the ORF comprises chemically-modified uracil residues.
17. The composition of claim 16 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine.
18. The composition of claim 4 , wherein the ORF comprises chemically-modified uracil residues.
19. The composition of claim 18 , wherein 100% of the uracil residues of the ORF comprises N1-methylpseudouridine.
20. The composition of claim 1 , wherein the Nipah virus F protein of the fusion protein comprises an amino acid sequence that has at least 90% identity with the amino acid sequence of SEQ ID NO: 13, and the Nipah virus G protein of the fusion protein comprises an amino acid sequence that has at least 90% identity with the amino acid sequence of SEQ ID NO: 11.