HERPES SIMPLEX VIRUS VACCINE
Provided herein are immunogenic compositions comprising mRNA encoding herpes simplex virus polypeptides, as well as methods of using the immunogenic compositions.
1 .- 71 . (canceled)
72 . A method of inducing an herpes simplex virus (HSV) antigen-specific immune response in a subject, the method comprising administering to the subject a composition comprising:
(a) a messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame (ORF) encoding at least one HSV antigenic polypeptide, 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,
to produce an HSV antigen-specific immune response in the subject.
73 . The method of claim 72 , wherein the HSV antigenic polypeptide comprises a herpes simplex virus 2 (HSV-2) glycoprotein B variant.
74 . The method of claim 73 , wherein the HSV-2 glycoprotein B variant comprises a transmembrane domain and a truncated C terminus, relative to a wild-type HSV-2 glycoprotein B.
75 . The method of claim 72 , wherein the HSV antigenic polypeptide comprises an HSV-2 glycoprotein C variant.
76 . The method of claim 75 , wherein the HSV-2 glycoprotein C variant comprises a transmembrane domain and a truncated C terminus, relative to a wild-type HSV-2 glycoprotein C;
77 . The method of claim 72 , wherein the HSV antigenic polypeptide comprises an HSV-2 glycoprotein D.
78 . The method of claim 72 , wherein 100% of the uracil in the ORF of the mRNA comprises a chemical modification.
79 . The method of claim 78 , wherein the chemical modification is 1-methylpseudouridine.
80 . The method of claim 73 , wherein the HSV-2 glycoprotein B variant comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 71.
81 . The method of claim 75 , wherein the HSV-2 glycoprotein C variant comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67.
82 . The method of claim 77 , wherein the HSV-2 glycoprotein D comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68.
83 . The method of claim 72 , wherein the subject is administered an mRNA having an ORF encoding an HSV-2 glycoprotein B variant comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 71, an mRNA having an ORF encoding an HSV-2 glycoprotein C variant comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and an mRNA having an ORF encoding an HSV-2 glycoprotein D comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68.
84 . The method of claim 72 , wherein the vaccine is administered to the subject by intradermal injection or intramuscular injection.
85 . The method of claim 72 , wherein the effective amount is a total dose of 25 μg-100 μg.
86 . The method of claim 85 , wherein the effective amount is a dose of 25 μg, 100 μg, 400 μg, or 500 μg administered to the subject a total of two times.
87 . The method of claim 72 , wherein the subject is immunocompromised.