Nucleic acid vaccines for varicella zoster virus (VZV)
Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having an open reading frame encoding at least one varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.
1. A messenger ribonucleic acid (mRNA) vaccine composition comprising;
(a) an mRNA polynucleotide comprising an open reading frame encoding a varicella zoster virus (VZV) gE protein; and
(b) a lipid nanoparticle,
wherein the lipid nanoparticle comprises 40-60 mol % ionizable cationic lipid, 5-15 mol % neutral lipid, 30-50 mol % cholesterol, and 0.5-3 mol % polyethylene glycol (PEG)-modified lipid.
2. The mRNA vaccine composition of claim 1 , wherein the open reading from which the mRNA polynucleotide is encoded is codon-optimized.
3. The mRNA vaccine composition of claim 1 , wherein the mRNA polynucleotide comprises a chemical modification.
4. The mRNA vaccine composition of claim 3 , wherein the chemical modification is selected from the group consisting of pseudouridine, 1-methylpseudouridine, 1-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.
5. The mRNA vaccine composition of claim 3 , wherein 100% of the uracil in the open reading frame comprises a chemical modification.
6. The mRNA vaccine composition of claim 3 , wherein the chemical modification is on carbon-5 of the uracil.
7. An engineered deoxyribonucleic acid (DNA) polynucleotide encoding the mRNA polynucleotide of the mRNA vaccine of claim 1 .
8. The mRNA vaccine composition of claim 1 , wherein the mRNA vaccine further comprises trisodium citrate buffer, sucrose and water.
9. The mRNA vaccine composition of claim 1 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
10. The mRNA vaccine composition of claim 1 , wherein the PEG-modified lipid is PEG-distearoyl glycerol (PEG-DMG).
11. A messenger ribonucleic acid (mRNA) vaccine composition comprising;
(a) an mRNA polynucleotide comprising an open reading frame (ORF) encoding a varicella zoster virus (VZV) gE protein and; a
(b) lipid nanoparticle,
wherein the lipid nanoparticle comprises 40-60 mol % ionizable cationic lipid, 5-15 mol % neutral lipid, 30-50 mol % cholesterol, and 0.5-3 mol % polyethylene glycol (PEG)-modified lipid, and
wherein 100% of uracil in the ORF comprises a 1-methylpseudouridine in the carbon-5 position of the uracil.
12. The mRNA vaccine composition of claim 11 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine and the PEG-modified lipid is PEG-distearoyl glycerol.
13. The mRNA vaccine composition of claim 1 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine and the PEG-modified lipid is PEG-distearoyl glycerol.
14. The mRNA vaccine composition of claim 1 , wherein the VZV gE protein comprises a Y569A mutation, relative to a wild-type VZV gE protein, wherein the wild-type VZV gE protein comprises the amino acid sequence of SEQ ID NO: 10.
15. The mRNA vaccine composition of claim 14 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.
16. The mRNA vaccine composition of claim 11 , wherein the VZV gE protein comprises a Y569A mutation, relative to a wild-type VZV gE protein, wherein the wild-type VZV gE protein comprises the amino acid sequence of SEQ ID NO: 10.
17. The mRNA vaccine composition of claim 16 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.
18. A messenger ribonucleic acid (mRNA) vaccine composition comprising:
(a) an mRNA polynucleotide comprising an open reading frame (ORF) encoding a varicella zoster virus (VZV) gE protein that comprises the amino acid sequence of SEQ ID NO: 38; and
(b) a lipid nanoparticle,
wherein the lipid nanoparticle comprises 40-60 mol % ionizable cationic lipid, 5-15 mol % DSPC lipid, 30-50 mol % cholesterol, and 0.5-3 mol % PEG-distearoyl glycerol, and
wherein 100% of uracil in the ORF comprises a 1-methylpseudouridine in the carbon-5 position of the uracil.