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 method comprising administering to a subject 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 in an effective amount to induce in the subject an immune response to the BetaCoV S protein or S protein subunit, wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % PEG-modified lipid.
2. The method of claim 1 , wherein the open reading frame encodes a BetaCoV S protein.
3. The method of claim 2 , wherein the immune response is a neutralizing antibody response specific to the BetaCoV S protein.
4. The method of claim 1 , wherein the open reading frame encodes a BetaCoV S protein subunit selected from an S1 subunit and an S2 subunit.
5. The method of claim 4 , wherein the immune response is a neutralizing antibody response specific to the BetaCoV S protein subunit.
6. The method of claim 1 , wherein the mRNA formulated in a lipid nanoparticle is administered intramuscularly.
7. The method of claim 1 , wherein the mRNA further comprises a 5′ untranslated region and a 3′ untranslated region.
8. The method of claim 1 , wherein the mRNA further comprises a poly(A) tail.
9. The method of claim 1 , wherein the mRNA further comprises a 5′ cap analog.
10. The method of claim 9 , wherein the 5′ cap analog is 7mG(5′)ppp(5′)NlmpNp.
11. The method of claim 1 , wherein the mRNA comprises a chemical modification.
12. The method of claim 11 , wherein the chemical modification is a 1-methylpseudouridine modification or a 1-ethylpseudouridine modification.
13. The method of claim 11 , wherein at least 80% of the uracil in the open reading frame of the mRNA has a chemical modification.
14. The method of claim 1 , wherein the lipid nanoparticle comprises 50 mol % ionizable cationic lipid, 10 mol % neutral lipid, 38.5 mol % cholesterol, and 1.5 mol % PEG-modified lipid.
15. The method of claim 1 , wherein the ionizable cationic lipid is Compound 25.
16. The method of claim 1 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and the PEG-modified lipid is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG-DMG).
17. A method comprising administering to a subject an mRNA comprising a 5′ cap analog, a 5′ untranslated region, an open reading frame encoding a BetaCoV S protein or S protein subunit, a 3′ untranslated region, and a poly(A) tail formulated in a lipid nanoparticle in an effective amount to induce in the subject an immune response to the BetaCoV S protein or S protein subunit, wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % PEG-modified lipid.
18. The method of claim 17 , wherein the open reading frame encodes a BetaCoV S protein.
19. The method of claim 18 , wherein the ionizable cationic lipid is Compound 25, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.
20. The method of claim 18 , wherein at least 80% of the uracil in the open reading frame of the mRNA has a 1-methylpseudouridine modification.
21. The method of claim 20 , wherein the ionizable cationic lipid is Compound 25, the neutral lipid is DSPC, and the PEG-modified lipid is PEG-DMG.