IMPROVED THERAPEUTIC COMPOSITION COMPRISING HEPATITIS B ANTIGEN HAVING S, PRE-S1 AND PRE-S2 PROTEIN, ALUMINIUM PHOSPHATE AND INTERFERON-ALPHA AND USE THEREOF FOR TREATMENT OF HEPATITIS B
The present disclosure provides compositions and methods useful for inducing an immune response and overcoming immune tolerance in a subject suffering from Hepatitis B. As described herein, the compositions of the disclosure comprise HBsAg having S, Pre-S1 and Pre-S2 proteins, an aluminum phosphate adjuvant and interferon-α.
1 . A therapeutic composition comprising:
(a) an HBsAg antigen comprising S protein, Pre-S1 protein and Pre-S2 protein;
(b) an aluminum phosphate adjuvant; and
(b) interferon-α,
wherein the composition comprises at least 20 μg of the HBsAg antigen and 1 MIU-6 MIU of the interferon-α.
2 . The therapeutic composition of claim 1 wherein the HBsAg antigen has an amino acid sequence at least 90% sequence identity to SEQ: ID NO 1.
3 . The therapeutic composition of claim 1 wherein the HBsAg antigen has an amino acid sequence at least 95% sequence identity to SEQ: ID NO 1.
4 . The therapeutic composition of claim 1 wherein the HBsAg antigen has an amino acid sequence of SEQ: ID NO 1.
5 . The therapeutic composition of any one of claims 1 to 4 wherein the composition comprises 3 MIU of the interferon-α.
6 . The therapeutic composition of any one of claims 1 to 5 wherein aluminum phosphate adjuvant is present in an amount of 500 μg.
7 . The therapeutic composition of any one of claims 1 to 6 wherein the composition comprises 40 μg of the HBsAg antigen.
8 . The therapeutic composition of claim 1 wherein the HBsAg antigen and interferon-α are present in a ratio of at least 20 μg of HBsAg antigen: 3 MIU interferon-α.
9 . The therapeutic composition of claim 1 wherein the HBsAg antigen and interferon-α are present in a ratio of 20 to 40 μg of HBsAg antigen: 1-6 MIU of interferon-α.
10 . The therapeutic composition of claim 1 wherein the HBsAg antigen and interferon-α are present in a ratio of 40 μg of HBsAg antigen: 3 MIU of interferon-α.
11 . The therapeutic composition of claim 1 for use inducing a Th1 cell response in a mammal.
12 . The therapeutic composition of claim 1 for use in overcoming immune tolerance in a subject suffering from chronic Hepatitis B.
13 . Use of the therapeutic composition of claim 1 for manufacture of a drug for inducing a Th1 cell response in a subject.
14 . The use of claim 13 wherein the subject has been infected with Hepatitis B.
15 . Use of the therapeutic composition of claim 1 for manufacture of a drug for overcoming immune tolerance in a subject suffering from chronic Hepatitis B.
16 . A pharmaceutical composition comprising the therapeutic composition of any one of claims 1 to 11 and a pharmaceutically acceptable excipient.
17 . The pharmaceutical composition of claim 11 for use in treating a subject suffering from Hepatitis B.
18 . A method of inducing a Th1 cell response in a mammal, said method comprising administering the therapeutic composition of claim 1 .
19 . A method of overcoming immune tolerance in a subject suffering from chronic Hepatitis B, said method comprising administering the therapeutic composition of any one of claims 1 to 12 .
20 . A method of treating Hepatitis B in a subject, said method comprising administering a therapeutically effective amount of the therapeutic composition of any one of claims 1 to 12 to the subject.
21 . The method of claim 20 wherein an additional Hepatitis B treatment is administered to the subject prior to, concurrently with, or after administration of the therapeutic composition to the subject.
22 . The method of claim 21 wherein the additional Hepatitis B treatment is a polymerase inhibitor, an RNase H inhibitor, a TLR agonist, an N-glycosylation inhibitor, an antisense oligonucleotide, an anti-hepatitis B antibody, a capsid inhibitor, a core protein inhibitor, a core assembly modulator, an S-antigen reducer or sequesterer, a nucleic acid polymers, a ccc DNA inhibitor, or an siRNA.
23 . A method of treating Hepatitis B in a subject, said method comprising combining an immunogenic composition comprising:
(i) an HBsAg antigen comprising S protein, Pre-S1 protein and Pre-S2 protein; and
(ii) an aluminum phosphate adjuvant,
with interferon-α to form an admixture, wherein the admixture comprises at least 20 μg of HBsAg antigen and 1 MIU-6 MIU of interferon-α and administering the admixture to a subject in need thereof.