METHODS AND COMPOSITIONS FOR ELICITING AN IMMUNE RESPONSE AGAINST HEPATITIS B VIRUS

• US 20120263755A1
• Filed: 04/16/2012
• Published: 10/18/2012
• Est. Priority Date: 04/14/2011
• Status: Active Grant

• Current Assignee: Dynamax Technologies Limited
• Original Assignee: Dynamax Technologies Limited
• Inventors: HEYWARD, William L.
• Granted Patent: US 9,452,212 B2
• Time in Patent Office: Days
• US Class Current: 424/227.1
• 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 diabetic human subject, comprising:

administering to a diabetic human subject a first and a second dose of an immunogenic composition on two separate occasions, wherein said immunogenic composition comprises a hepatitis B surface antigen (HBsAg) and an immunostimulatory sequence (ISS) of from 8 to 50 nucleotides in length comprising an unmethylated cytosine-phosphate-guanosine (CpG) motif,

wherein said HBsAg and said ISS are 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 by two months after said second dose.

2. The method of claim 1, wherein the ISS comprises the nucleotide sequence 5′

-TCG-3′

.

3. The method of claim 1, wherein the ISS comprises the nucleotide sequence ‘

5-CGTTCG-3’

.

4. The method of claim 1, wherein said ISS comprises the nucleotide sequence of SEQ ID NO:

1.

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

6. The method of claim 1, wherein said ISS comprises a phosphorothioate backbone modification.

7. The method of claim 1, wherein said ISS is single-stranded.

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

g of said HBsAg.

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

g of said ISS.

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

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

12. The method of claim 11, wherein said anti-HBsAg concentration is at least 15, 20, or 25 mIU/mL.

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

14. The method of claim 13, wherein said anti-HBsAg concentration is at least 20, 30, 40 or 50 mIU/mL.

15. The method of claim 1, wherein the diabetic human subject has type II diabetes.

16. The method of claim 15, wherein the subject is taking one or both of an oral hypoglycemic and insulin, at the onset of said administering.

17. The method of claim 16, 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.

18. The method of claim 1, wherein the diabetic human subject further has chronic kidney disease.

19. The method of claim 1, wherein said ISS is double-stranded.

20. A method for eliciting an immune response against hepatitis B virus (HBV) in a human subject who is a member of a hypo-responsive population, comprising:

administering to the human subject a first and a second dose of an immunogenic composition on two separate occasions, wherein the immunogenic composition comprises a hepatitis B surface antigen (HBsAg), and an immunostimulatory sequence (ISS) of from 8 to 50 nucleotides in length comprising an unmethylated cytosine-phosphate-guanosine (CpG) motif,

wherein the HBsAg and the ISS are present in the immunogenic composition in amounts effective to elicit an immune response comprising an anti-HBsAg concentration of at least 5 mUI/mL in the human subject by two months after the second dose.

21. The method of claim 20, wherein said hypo-responsive population comprises one or more of older adults, males, obese individuals, smokers, diabetics, and patients with chronic kidney disease.

22. The method of claim 20, wherein said immune response is a seroprotective immune response comprising an anti-HBsAg concentration of at least 10 mUI/mL in the human subject by two months after the second dose.

23. A method for eliciting a seroprotective immune response against hepatitis B virus (HBV) in a human subject with chronic kidney disease according to an abbreviated vaccination schedule, comprising:

administering to the human subject with chronic kidney disease an immunogenic composition according to an abbreviated vaccination schedule, wherein the abbreviated vaccination schedule comprises administering a first, second and third dose of the immunogenic composition on three separate occasions, wherein the immunogenic composition comprises a hepatitis B surface antigen (HBsAg), and an immunostimulatory sequence (ISS) of from 8 to 50 nucleotides in length comprising an unmethylated cytosine-phosphate-guanosine (CpG) motif,

wherein the HBsAg and the ISS are present in the immunogenic composition in amounts effective to elicit a seroprotective immune response comprising an anti-HBsAg concentration of at least 10 mUI/mL in the human subject by one month after the third dose.

24. A method for eliciting a durable immune response against hepatitis B virus (HBV) in a human subject with chronic kidney disease according to an abbreviated vaccination schedule, comprising:

administering to the human subject an immunogenic composition according to an abbreviated vaccination schedule, wherein the abbreviated vaccination schedule comprises administering a first, second and third dose of the immunogenic composition on three separate occasions, wherein the immunogenic composition comprises a hepatitis B surface antigen (HBsAg), and an immunostimulatory sequence (ISS) of from 8 to 50 nucleotides in length comprising an unmethylated cytosine-phosphate-guanosine (CpG) motif,

wherein the HBsAg and the ISS are present in the immunogenic composition in amounts effective to elicit a durable immune response comprising an anti-HBsAg concentration of at least 100 in the human subject 6 months or later after the third dose.

25. The method of claim 24, wherein said durable immune response comprises an anti-HBsAg concentration of at least 100 mIU/mL in the human subject at one month after said third dose.