Varicella zoster virus (VZV) vaccine
Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having a open reading reading frame encoding at least varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.
1. A vaccine composition comprising:(a) a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a varicella zoster virus (VZV) glycoprotein E (gE) or glycoprotein I (gI); and (b) a lipid nanoparticle comprising 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid, wherein the ionizable cationic lipid comprises a compound of Formula (I):
wherein
R 1 is selected from the group consisting of C 5-30 alkyl, C 5-20 alkenyl, and —R″M′R′;
R 2 and R 3 are independently selected from the group consisting of C 1-14 alkyl and C 2-14 alkenyl;
R 4 is —(CH 2 ) n Q, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R 5 is H;
each R 6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R 7 is H;
R is H;
R′ is selected from the group consisting of C 1-18 alkyl and C 2-18 alkenyl;
R″ is selected from the group consisting of C 3-14 alkyl and C 3-14 alkenyl; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
2. The composition of claim 1 , wherein the mRNA comprises a chemical modification.
3. The composition of claim 2 , wherein the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine, and 2′-O-methyl uridine.
4. The composition of claim 1 , wherein the lipid nanoparticle comprises 40-50 mol % cationic lipid, 5-15 mol % neutral lipid, 20-40 mol % cholesterol, and 0.2-4.5 mol % PEG-modified lipid.
5. The composition of claim 4 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine and the PEG-modified lipid is PEG-distearoyl glycerol.
6. The composition of claim 1 , wherein the open reading frame encodes VZV gE.
7. The composition of claim 6 , wherein the VZV gE protein comprises a Y569A mutation, relative to a wild-type VZV gE protein, and wherein the wild-type VZV gE protein comprises the amino acid sequence of SEQ ID NO: 10.
8. The composition of claim 7 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.
9. The composition of claim 1 , wherein the open reading frame encodes VZV gI.
10. The composition of claim 3 , wherein the chemical modification is N1-methylpseudouridine.
11. A vaccine composition comprising:(a) a chemically modified messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a varicella zoster virus (VZV) glycoprotein E (g E); and (b) a lipid nanoparticle comprising 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % cholesterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid, wherein the ionizable cationic lipid comprises a compound of Formula (I):
wherein
R 1 is selected from the group consisting of C 5-30 alkyl, C 5-20 alkenyl, and —R″M′R′;
R 2 and R 3 are independently selected from the group consisting of C 1-14 alkyl and C 2-14 alkenyl;
R 4 is —(CH 2 ) n Q, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R 5 is H;
each R 6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R 7 is H;
R is H;
R′ is selected from the group consisting of C 1-18 alkyl and C 2-18 alkenyl;
R″ is selected from the group consisting of C 3-14 alkyl and C 3-14 alkenyl; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
12. The composition of claim 11 , wherein the chemically modified mRNA comprises N1-methylpseudouridine.
13. The composition of claim 12 , wherein the lipid nanoparticle comprises 40-50 mol % cationic lipid, 5-15 mol % neutral lipid, 20-40 mol % cholesterol, and 0.2-4.5 mol % PEG-modified lipid.
14. The composition of claim 13 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine and the PEG-modified lipid is PEG-distearoyl glycerol.
15. The composition of claim 14 , wherein the VZV gE protein comprises a Y569A mutation, relative to a wild-type VZV gE protein, and wherein the wild-type VZV gE protein comprises the amino acid sequence of SEQ ID NO: 10.
16. The composition of claim 15 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.