Human cytomegalovirus RNA vaccines

Patent metadata

Field	Value
Publication number	US-10064935-B2
Application number	US-201715674569-A
Country	US
Kind code	B2
Filing date	Aug 11, 2017
Priority date	Oct 22, 2015
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

The disclosure describes HCMV ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

First claim

What is claimed is:

1. A human cytomegalovirus (hCMV) vaccine comprising:
(a) at least one messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide; (b) at least one mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide; (c) at least one mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide; (d) at least one mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide; (e) at least one mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide; and (f) at least one mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide, wherein the mRNA polynucleotides of (a)-(f) are formulated in at least one lipid nanoparticle that comprises a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid, in an effective amount to induce an immune response in a subject administered at least one dose of the vaccine, and wherein the mRNA polynucleotides of (a)-(f) are not self-replicating RNA.

2. The hCMV vaccine of claim 1 , wherein the at least one mRNA polynucleotide of (a)-(f) further encodes at least one 5′ terminal cap, 7mG(5′)ppp(5′)NlmpNp.

3. The hCMV vaccine of claim 1 , wherein at least 80% of the uracil in the open reading frame of (a)-(f) have a chemical modification selected from N1-methyl-pseudouridine or N1-ethyl-pseudouridine.

4. The hCMV vaccine of claim 3 , wherein the chemical modification is in the carbon-5 position of the uracil.

5. The hCMV vaccine of claim 1 , wherein the efficacy of the vaccine in vaccinated subjects is at least 60%, relative to unvaccinated subjects, following a single dose of the vaccine.

6. The hCMV vaccine of claim 5 , wherein the efficacy of the vaccine in vaccinated subjects is at least 70%, relative to unvaccinated subjects, following a single dose of the vaccine.

7. The hCMV vaccine of claim 6 , wherein the efficacy of the vaccine in vaccinated subjects is at least 80%, relative to unvaccinated subjects, following a single dose of the vaccine.

8. The hCMV vaccine of claim 7 , wherein the efficacy of the vaccine in vaccinated subjects is at least 90%, relative to unvaccinated subjects, following a single dose of the vaccine.

9. The hCMV vaccine of claim 1 , wherein the effective amount is sufficient to produce detectable levels of hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide as measured in serum of a subject vaccinated with at least one dose of the vaccine at 1-72 hours post administration.

10. The hCMV vaccine of claim 1 , wherein the effective amount is sufficient to produce a 1,000-10,000 neutralization titer produced by neutralizing antibody against the hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide as measured in serum of a subject vaccinated with at least one dose of the vaccine at 1-72 hours post administration.

11. The hCMV vaccine of claim 1 , wherein an anti-hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide antibody titer produced in a subject vaccinated with at least one dose of the vaccine is increased by at least 1 log relative to a control, wherein the control is an anti-hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide antibody titer produced in a subject who has not been administered a vaccine against hCMV.

12. The hCMV vaccine of claim 1 , wherein the anti-hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide antibody titer produced in a subject vaccinated with at least one dose of the vaccine is increased at least 2 times relative to a control, wherein the control is an anti-hCMV gH, gL, UL128, UL130, UL131A and/or gB polypeptide antibody titer produced in a subject who has not been administered a vaccine against hCMV.

13. The hCMV vaccine of claim 1 , wherein the effective amount is a total dose of 25 μg-200 μg.

14. The hCMV vaccine of claim 13 , wherein the effective amount is a total dose of 25 μg-100 μg.

15. The hCMV vaccine of claim 1 , wherein the ionizable cationic lipid comprises the following compound:

16. The hCMV vaccine of claim 1 , wherein the hCMV gH polypeptide comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 59, the hCMV gL polypeptide comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 61, the hCMV UL128 polypeptide comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 63, the hCMV UL130 polypeptide comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 65, the hCMV UL131A polypeptide comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 67, and/or the hCMV gB protein comprises an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO: 69.

17. The hCMV vaccine of claim 16 , wherein the hCMV gH polypeptide comprises the amino acid sequence identified by SEQ ID NO: 59, the hCMV gL polypeptide comprises the amino acid sequence identified by SEQ ID NO: 61, the hCMV UL128 polypeptide comprises the amino acid sequence identified by SEQ ID NO: 63, the hCMV UL130 polypeptide comprises the amino acid sequence identified by SEQ ID NO: 65, the hCMV UL131A polypeptide comprises the amino acid sequence identified by SEQ ID NO: 67, and/or the hCMV gB protein comprises the amino acid sequence identified by SEQ ID NO: 69.

18. The hCMV vaccine of claim 1 , wherein the at least one mRNA polynucleotide of (a) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 108, the at least one mRNA polynucleotide of (b) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 109, the at least one mRNA polynucleotide of (c) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 110, the at least one mRNA polynucleotide of (d) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 93, the at least one mRNA polynucleotide of (e) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 112, and/or the at least one mRNA polynucleotide of (f) comprises a sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO: 113.

19. A human cytomegalovirus (hCMV) vaccine comprising:
(a) at least one RNA polynucleotide comprising an open reading frame (ORF) that comprises the nucleotide sequence identified by SEQ ID NO: 108, (b) at least one RNA polynucleotide comprising an ORF that comprises the nucleotide sequence identified by SEQ ID NO: 109, (c) at least one RNA polynucleotide comprising an ORF that comprises the nucleotide sequence identified by SEQ ID NO: 110, (d) at least one RNA polynucleotide comprising an ORF that comprises the nucleotide sequence identified by SEQ ID NO: 93, (e) at least one RNA polynucleotide comprising an ORF that comprises the nucleotide sequence identified by SEQ ID NO: 112, and (f) at least one RNA polynucleotide comprising an ORF that comprises the nucleotide sequence identified by SEQ ID NO: 113, wherein the RNA polynucleotides of (a)-(f) are formulated in at least one lipid nanoparticle that comprises a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipi

Assignees

• Modernatx Inc

Inventors

• Ciaramella Giuseppe
• John Shinu
• Mousavi Kambiz

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/22

  for herpes viruses · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07K14/005

  from viruses · CPC title

• C07K2319/02

  containing a signal sequence · CPC title