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

• US 20180243407A1
• Filed: 01/18/2018
• Published: 08/30/2018
• 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 10,314,907 B2
• Time in Patent Office: Days
• 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

1-19. -19. (canceled)

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 comprising a hepatitis B surface antigen (HBsAg) and an immunostimulatory sequence (ISS) 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 at two months after only two doses,

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

1, and 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, and wherein said hypo-responsive population comprises one or more of older adults, obese individuals, smokers, patients with chronic liver disease, and hepatitis C virus (HCV)-infected individuals.

21. The method of claim 20, wherein said hypo-responsive population comprises one or more of older adults, obese individuals, and smokers.

22. The method of claim 20, wherein said hypo-responsive population comprises one or both of patients with chronic liver disease, and hepatitis C virus (HCV)-infected individuals.

26. The method of claim 20, wherein said ISS comprises a phosphate backbone modification.

27. The method of claim 26, wherein said phosphate backbone modification comprises a phosphorothioate backbone modification.

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

g of said HBsAg and about 3000 μ

g of said ISS.

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

g of said HBsAg.

30. The method of claim 20, wherein said immunogenic composition comprises about 3000 μ

g of said ISS.

31. The method of claim 20, wherein said HBsAg is a recombinant HBsAg produced in yeast.

32. The method of claim 20, 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.

33. The method of claim 20, wherein said vaccination schedule has a satisfactory safety profile.

23-25. -25. (canceled)