Herpes simplex virus vaccine
Herpes simplex virus (HSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In a preferred embodiment, the vaccine is formulated as a lipid nanoparticle comprising at least one cationic lipid.
1. A messenger ribonucleic acid (mRNA) vaccine composition comprising:
(a) an mRNA polynucleotide having an open reading frame (ORF) encoding an HSV-2 glycoprotein B variant that comprises a transmembrane domain and is truncated at its C terminus, relative to a wild-type HSV-2 glycoprotein B;
(b) an mRNA polynucleotide having an ORF encoding an HSV-2 glycoprotein C variant that comprises a transmembrane domain and is truncated at its C terminus, relative to a wild-type HSV-2 glycoprotein C;
(c) an mRNA polynucleotide having an ORF encoding an HSV-2 glycoprotein D; and
(d) a lipid nanoparticle comprising 20-60% ionizable cationic lipid, 0.5-15% polyethylene glycol (PEG)-modified lipid, 25-55% cholesterol, and 5-25% neutral lipid,
wherein the ionizable lipid comprises a compound of Formula (I):
or a salt or isomer thereof, wherein:
R 1 is R″M′R′ or C 5-20 alkenyl;
R 2 and R 3 are each independently selected from C 1-14 alkyl and C 2-14 alkenyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is selected from 3, 4, and 5;
M and M′ are each independently —OC(O)— or —C(O)O—;
R 5 , R 6 , and R 7 are each H;
R′ is a linear C 1-12 alkyl, or C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl;
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
2. The mRNA vaccine composition of claim 1 , wherein the mRNA vaccine composition further comprises an mRNA comprising an ORF encoding an HSV-2 ICP0, and an mRNA comprising an ORF encoding an HSV-2 ICP4.
3. The mRNA vaccine composition of claim 1 , wherein the ionizable cationic lipid comprises Compound 25:
4. The mRNA vaccine composition of claim 1 , wherein:
R 1 is R′″M′R′;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 4;
M and M′ are each independently —OC(O)—;
R 5 , R 6 , and R 7 are each H;
R′ is C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl; and
m is 6.
5. The mRNA vaccine composition of claim 1 , wherein:
R 1 is C 5-20 alkenyl;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 3;
M is —C(O)O—;
R 5 , R 6 , and R 7 are each H; and
m is 6.
6. The mRNA vaccine composition of claim 1 , wherein 100% of uracil nucleotides in the ORFs comprise 1-methylpseudouridine.
7. The mRNA vaccine composition of claim 6 , wherein the ionizable cationic lipid comprises Compound 25:
8. The mRNA vaccine composition of claim 6 , wherein:
R 1 is R″M′R′;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 4;
M and M′ are each independently —OC(O)—;
R 5 , R 6 , and R 7 are each H;
R′ is C 1-12 alkyl substituted with C 6-9 alkyl;
R″ is C 3-14 alkyl; and
m is 6.
9. The mRNA vaccine composition of claim 6 , wherein:
R 1 is C 5-20 alkenyl;
R 2 and R 3 are each independently C 1-14 alkyl;
R 4 is —(CH 2 ) n Q, wherein Q is OH and n is 3;
M is —C(O)O—;
R 5 , R 6 , and R 7 are each H; and
m is 6.