Nucleic acid vaccines for varicella zoster virus (vzv)

Abstract

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 .- 62 . (canceled) 
     
     
         63 . A method of inducing an antigen-specific immune response in a subject, the method comprising administering to the subject a varicella zoster virus (VZV) vaccine in an amount effective to produce an antigen-specific immune response in the subject, wherein the VZV vaccine comprises (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a VZV glycoprotein selected from VZV gE, gI, gB, gH, gK, gL, gC, gN, and gM and (b) a lipid nanoparticle, and the lipid nanoparticle comprises 40-60 mol % ionizable cationic lipid, 5-15 mol % neutral lipid, 30-50 mol % sterol, and 0.5-3 mol % polyethylene glycol (PEG)-modified lipid. 
     
     
         64 . The method of  claim 63 , wherein the antigen specific immune response comprises a T cell response or a B cell response. 
     
     
         65 . The method of  claim 63 , wherein the subject is administered a single dose of the vaccine. 
     
     
         66 . The method of  claim 63 , wherein the subject is administered a first dose and a second (booster) dose of the vaccine. 
     
     
         67 . The method of  claim 63 , wherein the vaccine is administered to the subject by intramuscular injection. 
     
     
         68 .- 78 . (canceled) 
     
     
         79 . The method of  claim 63 , wherein the effective amount is 50 μg-1000 μg. 
     
     
         80 . The method of  claim 79 , wherein the effective amount is a dose of 25 μg, 100 μg, 400 μg, or 500 μg. 
     
     
         81 .- 84 . (canceled) 
     
     
         85 . The method of  claim 63 , wherein the subject is infected with a VZV virus. 
     
     
         86 . The method of  claim 63 , wherein the subject is immunocompromised. 
     
     
         87 .- 112 . (canceled) 
     
     
         113 . The method of  claim 63 , wherein the mRNA polynucleotide comprises a chemical modification. 
     
     
         114 . The method of  claim 63 , 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. 
     
     
         115 . The method of  claim 63 , wherein 100% of the uracil in the open reading frame comprises a chemical modification. 
     
     
         116 . The method of  claim 63 , wherein the chemical modification is methylpseudouridine. 
     
     
         117 . The method of  claim 63 , wherein the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). 
     
     
         118 . The method of  claim 63 , wherein the sterol is cholesterol. 
     
     
         119 . The method of  claim 63 , wherein the PEG-modified lipid is PEG-distearoyl glycerol (PEG-DMG). 
     
     
         120 . The method of  claim 63 , wherein the neutral lipid is DSPC, the sterol is cholesterol, and the PEG-modified lipid PEG-DMG. 
     
     
         121 . The method of  claim 63 , wherein the VZV glycoprotein is a VZV gE protein. 
     
     
         122 . The method of  claim 121 , wherein the VZV gE protein comprises a Y569A mutation, relative to a wild-type VZV gE protein, and the wild-type VZV gE protein comprises the amino acid sequence of SEQ ID NO: 10. 
     
     
         123 . The method of  claim 122 , wherein the VZV gE protein comprises the amino acid sequence of SEQ ID NO: 38.