Betacoronavirus mRNA vaccine
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 composition, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle.
2. The composition of claim 1 , wherein the open reading frame encodes a BetaCoV S protein.
3. The composition of claim 1 , wherein the open reading frame encodes an S protein subunit selected from an S1 subunit and an S2 subunit.
4. The composition of claim 1 , wherein the mRNA further comprising a 5′ untranslated region (UTR) and a 3′ UTR.
5. The composition of claim 4 , wherein the mRNA further comprises a poly(A) tail.
6. The composition of claim 4 , wherein the mRNA further comprises a 5′ cap analog.
7. The composition of claim 6 , wherein the 5′ cap analog is 7mG(5′)ppp(5′)NlmpNp.
8. The composition of claim 1 , wherein the mRNA comprises a chemical modification.
9. The composition of claim 8 , wherein the chemical modification is a 1-methylpseudouridine modification or a 1-ethylpseudouridine modification.
10. The composition of claim 8 , wherein at least 80% of the uracil in the open reading frame has a chemical modification.
11. The composition of claim 1 , wherein the lipid nanoparticle comprises an ionizable cationic lipid, a neutral lipid, a sterol, and a PEG-modified lipid.
12. The composition of claim 11 , wherein the lipid nanoparticle comprises 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-15% PEG-modified lipid.
13. The composition of claim 12 , wherein the lipid nanoparticle comprises 50% ionizable cationic lipid, 10% neutral lipid, 38.5% sterol, and 1.5% PEG-modified lipid.
14. The composition of claim 11 , wherein the ionizable cationic lipid is Compound 25.
15. The composition of claim 11 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), the sterol is cholesterol, and the PEG-modified lipid is 1,2-dimyristoyl-racalycero-3-methoxypolyethylene glycol-2000 (PEG-DMG) or PEG-cDMA.
16. A composition, comprising: a messenger ribonucleic acid (mRNA) comprising a 5′ untranslated region (UTR), an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit, a 3′ UTR, and a poly(A) tail, formulated in a lipid nanoparticle that comprises 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-15% PEG-modified lipid.
17. The composition of claim 16 , wherein the open reading frame encodes a BetaCoV S protein.
18. The composition of claim 16 , wherein the open reading frame encodes an S protein subunit selected from an S1 subunit and an S2 subunit.
19. The composition of claim 16 , wherein the mRNA further comprises 5′ cap analog 7mG(5′)ppp(5′)NlmpNp.
20. The composition of claim 16 , wherein at least 80% of the uracil in the open reading frame has a chemical modification.
21. The composition of claim 20 , wherein the chemical modification is a 1-methylpseudouridine modification or a 1-ethylpseudouridine modification.
22. The composition of claim 16 , wherein the ionizable cationic lipid is Compound 25.
23. The composition of claim 16 , wherein the neutral lipid is DSPC, the sterol is cholesterol, and the PEG-modified lipid is PEG-DMG.
24. A composition, comprising: a messenger ribonucleic acid (mRNA) comprising a 5′ cap analog, a 5′ untranslated region (UTR), an open reading frame encoding a betacoronavirus (BetaCoV) S protein, a 3′ UTR, and a poly(A) tail, formulated in a lipid nanoparticle that comprises 20-60% ionizable cationic lipid, 5-25% DSPC, 25-55% cholesterol, and 0.5-15% PEG-DMG, wherein the ionizable cationic lipid has the structure of Compound 25, and wherein at least 80% of the uracil in the open reading frame has a 1-methylpseudouridine modification.
25. The composition of claim 24 , wherein the 5′ cap analog is 7mG(5′)ppp(5′)NlmpNp.
26. A lipid nanoparticle, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit; wherein the lipid nanoparticle comprises 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-15% PEG-modified lipid.