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) a mRNA polynucleotide comprising an open reading frame (ORF) encoding a varicella zoster virus (VZV) gE protein, wherein the ORF comprises a sequence comprising at least 90% sequence identity to the mRNA sequence of SEQ ID NO. 62; 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 ORF 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 1 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.
6 . The mRNA vaccine composition of claim 1 , wherein the mRNA vaccine further comprises trisodium citrate buffer, sucrose and water.
7 . The mRNA vaccine composition of claim 1 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
8 . The mRNA vaccine composition of claim 1 , wherein the PEG-modified lipid is PEG-distearoyl glycerol (PEG-DMG).
9 . 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.
10 . A messenger ribonucleic acid (mRNA) vaccine composition comprising;
(a) a mRNA polynucleotide comprising an open reading frame (ORF) encoding a varicella zoster virus (VZV) gE protein, wherein the ORF comprises a sequence comprising at least 90% sequence identity to the ORF of SEQ ID NO. 101, wherein the mRNA polynucleotide comprises a chemical modification; 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.
11 . The mRNA vaccine composition of claim 10 , 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.
12 . The mRNA vaccine composition of claim 10 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.