Immunogenicity of a cpg-adjuvanted herpes zoster vaccine

Patent metadata

Field	Value
Publication number	US-2025163105-A1
Application number	US-202218723407-A
Country	US
Kind code	A1
Filing date	Dec 22, 2022
Priority date	Dec 23, 2021
Publication date	May 22, 2025
Grant date	—

Abstract

The present disclosure relates to methods for increasing cell-mediated immunity against varicella zoster virus (VZV) in a human subject in need thereof by administration of an immunogenic composition comprising effective amounts of a VZV glycoprotein E antigen and an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for prevention of herpes zoster and/or postherpetic neuralgia.

First claim

What is claimed:

1 . A method of increasing cell-mediated immunity against varicella zoster virus (VZV) in a human subject in need thereof, the method comprising:
administering to the human subject an immunogenic composition comprising: i) an unmethylated cytidine-phospho-guanosine (CpG)-containing oligonucleotide comprising the sequence of 5′-TGACTGTGAA CGTTCGAGAT GA-3′(SEQ ID NO: 1); and ii) a truncated VZV glycoprotein E (gE) antigen, which are present in the immunogenic composition in amounts effective to increase cell-mediated immunity against VZV relative to cell-mediated immunity against VZV in the subject prior to administration of the immunogenic composition, wherein a first dose and a second dose of the immunogenic composition is administered to the human subject, with the second dose administered from 2 months to 6 months after the first dose.

2 . The method of claim 1 , wherein the immunogenic composition comprises: from about 25 μg to about 150 μg of the gE antigen, and from about 750 μg to about 6000 μg of the oligonucleotide.

3 . The method of claim 1 , wherein the immunogenic composition comprises from about 50 μg to about 100 μg of the gE antigen, and from about 1500 μg to about 6000 μg of the oligonucleotide.

4 . The method of claim 1 , wherein the immunogenic composition comprises about 25 μg, about 50 μg, about 75 μg, about 100 μg, about 125 μg, or about 150 μg of the gE antigen, and about 750 μg, about 1500 μg, about 3000 μg, or about 6000 μg of the oligonucleotide.

5 . The method of claim 4 , wherein the immunogenic composition comprises about 100 μg of the gE antigen, and about 3000 μg or 6000 μg of the oligonucleotide.

6 . A method of increasing an immune response against varicella zoster virus (VZV) in a human subject in need thereof, the method comprising:
administering to the human subject an immunogenic composition comprising: i) an unmethylated cytidine-phospho-guanosine (CpG)-containing oligonucleotide comprising the sequence of 5′-TGACTGTGAA CGTTCGAGAT GA-3′(SEQ ID NO: 1); and ii) a truncated VZV glycoprotein E (gE) antigen, wherein the immunogenic composition comprises about 100 μg of the gE antigen and about 3000 μg or about 6000 μg of the oligonucleotide.

7 . The method of claim 5 or claim 6 , wherein the immunogenic composition comprises about 100 μg of the gE antigen, and about 3000 μg of the oligonucleotide.

8 . The method of claim 5 or claim 6 , wherein the immunogenic composition comprises about 100 μg of the gE antigen, and about 6000 μg of the oligonucleotide.

9 . The method of any one of claims 1-8 , wherein the oligonucleotide comprises at least one phosphorothioate linkage, or wherein all nucleotide linkages are phosphorothioate linkages.

10 . The method of any one of claims 1-9 , wherein the oligonucleotide is a single-stranded oligodeoxynucleotide.

11 . The method of any one of claims 1-10 , wherein the gE antigen is a recombinant protein devoid of transmembrane and intravirion domains of a full-length VZV gE antigen.

12 . The method of claim 11 , wherein the gE antigen comprises the amino acid sequence of SEQ ID NO:4, or an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:4.

13 . The method of claim 11 , wherein the gE antigen comprises the amino acid sequence of SEQ ID NO:5, or an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:5.

14 . The method of any one of claims 11-13 , wherein the recombinant protein is produced in mammalian cells.

15 . The method of any one of claims 1-14 , wherein the immunogenic composition further comprises an aluminum salt adjuvant.

16 . The method of claim 15 , wherein the aluminum salt adjuvant comprises one or more of the group consisting of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate.

17 . The method of claim 15 , wherein the aluminum salt adjuvant comprises aluminum hydroxide.

18 . The method of any one of claims 15-17 , wherein the immunogenic composition comprises from about 0.25 mg to about 1.25 mg Al 3+ .

19 . The method of any one of claims 15-17 , wherein the immunogenic composition comprises about 0.50 mg, about 0.75 mg, or about 1.00 mg Al 3+ .

20 . The method of claim 19 , wherein the immunogenic composition comprises about 0.75 mg Al 3+ .

21 . The method of any one of claims 15-20 , wherein the immunogenic composition further comprises a pharmaceutically acceptable buffer.

22 . The method of claim 21 , wherein the buffer is not a phosphate-containing buffer.

23 . The method of claim 21 , wherein the buffer is a Tris buffer.

24 . The method of any one of claims 1-23 , wherein the immunogenic composition does not comprise one or more of a saponin, a TLR4 agonist, and a liposome.

25 . The method of any one of claims 1-23 , wherein the immunogenic composition does not comprise one or more of QS21, 3-O-deacylated monophosphoryl lipid A (3D-MPL1), dioleoyl phosphatidylcholine, and cholesterol.

26 . The method of any one of claims 1-25 , wherein the gE antigen and the oligonucleotide are present in the immunogenic composition at a ratio of from 1:15 to 1:120 (wt/wt), optionally wherein the gE antigen and the oligonucleotide are present in the immunogenic composition at a ratio of from 1:15 to 1:60 (wt/wt).

27 . The method of any one of claims 1-26 , wherein the gE antigen and the oligonucleotide are present in the immunogenic composition at a ratio of about 1:15, about 1:20, about 1:30, about 1:40, about 1:60, about 1:80, or about 1:120 (wt/wt), optionally wherein the gE antigen and the oligonucleotide are present in the immunogenic composition at a ratio of about 1:30 (wt/wt) or about 1:60 (wt/wt).

28 . The method of any one of claims 21-27 , wherein the oligonucleotide and the Al3+ are present in the immunogenic composition at a ratio of from 8:1 to 2:1 (wt/wt), optionally wherein the oligonucleotide and the Al 3+ are present in the immunogenic composition at a ratio of about 8:1 (wt/wt) or about 4:1 (wt/wt).

29 . The method of any one of claims 1-28 , wherein the human subject is 18 years of age or older.

30 . The method of any one of claims 1-29 , wherein the human subject is 50 years of age or older.

31 . The method of claim 30 , wherein the human subject is 50-69 years of age.

32 . The method of any one of claims 1-31 , wherein the human subject is suspected to have a latent VZV infection.

33 . The method of any one of claims 1-32 , wherein the human subject was not previously vaccinated against varicella or herpes zoster.

34 . The method of any one of claims 6-33 , wherein the human subject receives a first dose and a second dose of the immunogenic composition with the second dose administered from 1 month to 1 year after the first dose.

35 . The method of claim 34 , wherein the second dose is administered from 2 months to 6 months after the first dose.

36 . The method of any one of claims 1-5 and 35 , wherein the second dose is administered about 2 months after the first dose.

37 . The method of any one of claims 1-36 , wherein the immunogenic composition is administer

Assignees

• Dynavax Tech Corp

Inventors

• Janssen Robert S

Classifications

• C12N2710/16771

  Demonstrated in vivo effect · CPC title

• C12N2710/16734

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2710/16722

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title