Human cytomegalovirus vaccine

Patent metadata

Field	Value
Publication number	US-11406703-B2
Application number	US-202117411896-A
Country	US
Kind code	B2
Filing date	Aug 25, 2021
Priority date	Aug 25, 2020
Publication date	Aug 9, 2022
Grant date	Aug 9, 2022

Abstract

Aspects of the disclosure relate to methods for producing an antigen-specific immune response to human cytomegalovirus (hCMV) in a subject by administering mRNA vaccines.

First claim

What is claimed is:

1. A human cytomegalovirus (hCMV) immunogenic composition comprising (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide; (b) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide; (c) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide; (d) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide; (e) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide; and (f) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide, wherein:
the molar ratio of (a):(f) within the immunogenic composition is about 1:1;
the molar ratio of (b):(c):(d):(e) within the immunogenic composition is about 1:1:1:1; and
the molar ratio of each of (a) and (f) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1.

2. The hCMV immunogenic composition of claim 1 , wherein the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2.

3. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition is maintained as a liquid formulation until use in administration to patients.

4. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition is maintained as a lyophilized formulation until use in administration to patients.

5. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition is stable for at least three months when stored at a temperature of greater than 0° C. and less than or equal to 10° C.

6. The hCMV immunogenic composition of claim 5 , wherein the hCMV immunogenic composition is stable for at least twelve to eighteen months when stored at a temperature of greater than 0° C. and less than or equal to 10° C.

7. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition is stable for at least three months when stored at a temperature of about 5° C.

8. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition has increased stability relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses.

9. The hCMV immunogenic composition of claim 8 , wherein the hCMV immunogenic composition has increased stability when stored for at least three months, or at least twenty-four months, at a temperature of greater than 0° C. and less than or equal to 10° C. relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses.

10. The hCMV immunogenic composition of claim 1 , wherein the hCMV immunogenic composition has:
(i) increased pentamer expression relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses;
(ii) increased pentamer antibody levels relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses;
(iii) increased gB expression relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses; and/or
(iv) increased gB antibody levels relative to an hCMV immunogenic composition in which (a)-(f) are present in approximately equivalent masses.

11. The hCMV immunogenic composition of claim 1 , wherein the mRNA polynucleotides of (a)-(f) are formulated in at least one lipid nanoparticle in an amount sufficient to induce an antigen-specific immune response to hCMV or a hCMV antigen in a subject.

12. The hCMV immunogenic composition of claim 1 , wherein the mRNA polynucleotides of (a)-(f) are formulated in at least one lipid nanoparticle and lyophilized in an amount sufficient to induce an antigen-specific immune response to hCMV or a hCMV antigen in a subject.

13. The hCMV immunogenic composition of claim 1 , wherein at least one of the mRNA polynucleotides of (a)-(f) comprises a chemical modification.

14. The hCMV immunogenic composition of claim 13 , wherein at least 80% of the uracil in the open reading frame of mRNA polynucleotides (a)-(f) have a chemical modification selected from N1-methyl-pseudouridine or N1-ethyl-pseudouridine.

15. The hCMV immunogenic composition of claim 14 , wherein the chemical modification is in the carbon-5 position of the uracil.

16. The hCMV immunogenic composition of claim 1 , wherein at least one of the mRNA polynucleotides of (a)-(f) further comprises at least one 5′ terminal cap, and wherein the 5′ terminal cap is 7mG(5′)ppp(5′)N1mpNp.

17. The hCMV immunogenic composition of claim 11 , wherein the lipid nanoparticle comprises a mixture of lipids comprising: an ionizable amino lipid; cholesterol; 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); and 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (DMG-PEG).

18. The hCMV immunogenic composition of claim 17 , wherein the ionizable amino lipid comprises Compound I:

19. The hCMV immunogenic composition of claim 17 , wherein the lipid nanoparticle comprises a mixture of lipids comprising 20-60 mol % ionizable amino lipid, 25-55 mol % cholesterol, 5-25 mol % DSPC, and 0.5-15 mol % DMG-PEG.

20. The hCMV immunogenic composition of claim 19 , wherein the lipid nanoparticle comprises a mixture of lipids comprising 45-55 mol % ionizable amino lipid, 35-40 mol % cholesterol, 5-15 mol % DSPC, and 1-2 mol % DMG-PEG.

21. The hCMV immunogenic composition of claim 1 , wherein the molar ratio of mRNAs (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2 and results in 10% less lipid administered to patients compared to when an equal mass of mRNAs (a):(b):(c):(d):(e):(f) is administered.

22. The hCMV immunogenic composition of claim 1 , wherein the mRNA encoding hCMV gH protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 5, the mRNA encoding hCMV gL protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 6, the mRNA encoding hCMV UL128 protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 2, the mRNA encoding hCMV UL130 protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 3, the mRNA encoding hCMV UL131A protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 4, and/or the mRNA encoding hCMV gB protein comprises a nucleotide sequence having at least 90% identity to the nucleotide sequence of sequence of SEQ ID NO: 1.

23. The hCMV immunogenic composition of claim 22 , wherein the mRNA encoding hCMV gH protein comprises the nucleotide sequence of sequence of SEQ ID NO: 5, the mRNA encoding hCMV gL protein comprises the nucleotide sequence of sequence of SEQ ID NO: 6, the mRNA encoding hCMV UL128 protein comprises the nucleotide sequence of sequence of SEQ ID NO: 2, the mRNA encoding hCMV UL130 protein comprises the nucleotide sequence of sequence of SEQ ID NO: 3, the mRNA encoding hCMV UL131A protein comprises the nucleotide sequence of sequence of SEQ ID NO: 4, and/or the mRNA encoding hCMV gB protein comprises the nucleotide sequence of sequence of SEQ ID NO: 1.

24. The hCMV immunogenic composition of claim 1 , wherein the open re

Assignees

• Modernatx Inc

Inventors

• Kramarczyk Jack F
• Hassett Kimberly
• John Shinu
• White Phil
• Carfi Andrea

Classifications

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K39/245 Primary

  Herpetoviridae, e.g. herpes simplex virus · CPC title

• A61K31/7115

  Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine · CPC title

• C12N2710/16111

  Cytomegalovirus, e.g. human herpesvirus 5 · CPC title

• A61K2039/55566

  Emulsions, e.g. Freund's adjuvant, MF59 · CPC title