Methods and compositions for eliciting an immune response against hepatitis B virus

• US 9,452,212 B2
• Filed: 04/16/2012
• Issued: 09/27/2016
• Est. Priority Date: 04/14/2011
• Status: Active Grant

• Current Assignee: Dynamax Technologies Limited
• Original Assignee: Dynamax Technologies Limited
• Inventors: Heyward, William L.
• Primary Examiner(s): Gill, Rachel B
• Application Number:
  US13/448,302
• Publication Number:
  US 20120263755A1
• Time in Patent Office: 1,625 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/42 viral
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/08 against material from viruses
• CPC Class Codes: C07K 16/082 Hepadnaviridae, e.g. hepatitis B virus
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2730/10134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2730/10171 : Demonstrated in vivo effect
• CPC Class Codes: C12N 2770/20033 : Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention relates to immunization of hypo-responsive groups of individuals. In particular, the present invention provides methods and compositions for eliciting a potent immune response to hepatitis B virus in individuals in need thereof.

Claims

1. A method for eliciting a seroprotective immune response against hepatitis B virus (HBV) in a human subject with type II diabetes and without chronic kidney disease, comprising:

administering to the human subject a first and a second dose of an immunogenic composition comprising a hepatitis B surface antigen (HBsAg) and an immunostimulatory sequence (ISS) present in said immunogenic composition in amounts effective to elicit a seroprotective immune response comprising an anti-HBsAg concentration of at least 10 mIU/mL in the subject at one month after only two doses,

wherein said ISS is single stranded and consists of the nucleotide sequence of SEQ ID NO;

1, and wherein said immunogenic composition comprises from about 10 to about 20 μ

g of said HBsAg and from about 1000 to about 3000 μ

g of said ISS.

2. The method of claim 1, wherein the human subject is an adult over 40 years of age.

3. The method of claim 1, wherein said ISS comprises a phosphate backbone modification.

4. The method of claim 3, wherein said phosphate backbone modification comprises a phosphorothioate backbone modification.

5. The method of claim 1, wherein said immunogenic composition comprises about 20 μ

g of said HBsAg and about 3000 μ

g of said ISS.

6. The method of claim 1, wherein said immunogenic composition comprises about 20 μ

g of said HBsAg.

7. The method of claim 1, wherein said immunogenic composition comprises about 3000 μ

g of said ISS.

8. The method of claim 1, wherein said HBsAg is a recombinant HBsAg produced in yeast.

9. The method of claim 1, wherein said seroprotective immune response comprises an anti-HBsAg concentration of at least 20 mIU/mL in the subject at one month after said second dose.

10. The method of claim 1, wherein said seroprotective immune response comprises an anti-HBsAg concentration of at least 25 mIU/mL in the subject at two months after said second dose.

11. The method of claim 1, wherein said seroprotective immune response comprises an anti-HBsAg concentration of at least 50 mIU/mL in the subject at six months after said second dose.

12. The method of claim 1, wherein the subject is taking one or both of an oral hypoglycemic and insulin, at the onset of said administering.

13. The method of claim 12, wherein the oral hypoglycemic comprises one or more of the group consisting of a biguanide, a sulfonylurea, a nonsulfonylurea secretagogue, an alpha glucosidase inhibitor, and a thiazolidinedione.

14. The method of claim 1, wherein said immunogenic composition comprises from 10 to 20 μ

g of said HBsAg and from 1000 to 3000 μ

g of said ISS.

15. The method of claim 1, wherein the human subject is from 41 to 60 years of age.