IMMUNOGENIC COMPOSITIONS FOR TREATMENT OF HEPATITIS B
The present disclosure provides compositions and methods useful for inducing a Th1 cell response 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 and an aluminum phosphate adjuvant. In a preferred embodiment, the immunogenic composition comprises at least 20 μg/ml of HBsAg antigen and the amount of non-adsorbed antigen is at least 30%.
1 - 15 . (canceled)
16 . An immunogenic composition comprising:
(a) an HBsAg antigen comprising S protein, Pre-S1 protein and Pre-S2 protein; and
(b) an aluminum phosphate adjuvant,
wherein the composition comprises at least 20 μg/ml of HBsAg antigen and the weight ratio of the HBsAg antigen to the amount of aluminum present in the adjuvant is from about 40:62.5 to about 20:500.
17 . The immunogenic composition according to claim 16 , wherein the weight ratio is about 20:500.
18 . The immunogenic composition according to claim 16 , wherein the weight ratio is about 40:500.
19 . The immunogenic composition according to claim 16 , wherein the weight ratio is 60:500.
20 . The immunogenic composition according to claim 16 , wherein the aluminum is present in a concentration of about 500 μg/ml.
21 . The immunogenic composition according to claim 16 , wherein the HBsAg antigen in a concentration of about 20 μg/ml.
22 . The immunogenic composition according to claim 16 , wherein the HBsAg antigen in a concentration of about 40 μg/ml.
23 . The immunogenic composition according to claim 16 , wherein the HBsAg antigen in a concentration of about 60 μg/ml.
24 . A pharmaceutical composition comprising the immunogenic composition of claim 16 and a pharmaceutically acceptable excipient.
25 . A method of inducing a Th1 cell response in a mammal, said method comprising administering the immunogenic composition of claim 16 .
26 . A method of treating Hepatitis B in a subject, said method comprising administering a therapeutically effective amount of the immunogenic composition of claim 16 to the subject.
27 . The method of claim 26 , wherein an additional Hepatitis B treatment is administered to the subject prior to, concurrently with, or after administration of the immunogenic composition to the subject.
28 . The method of claim 27 , wherein the additional Hepatitis B treatment is a nucleoside inhibitor or a pegylated interferon alpha.
29 . The method of claim 27 , 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, an interferon, an immune modulator or an siRNA.
30 . An aqueous pharmaceutical composition comprising
(a) an HBsAg antigen in a concentration of at least 20 μg/ml HBsAg antigen; and
(b) an aluminum phosphate adjuvant,
wherein the aluminum is present in a concentration of at least 500 μg/ml and the amount of non-adsorbed antigen is at least 30% in the aqueous pharmaceutical composition.
31 . The aqueous pharmaceutical composition according to claim 30 , wherein the HBsAg antigen comprises an S protein having at least 90% identity to the amino acid sequence of SEQ ID NO:1.
32 . The aqueous pharmaceutical composition according to claim 30 , wherein the HBsAg antigen comprises S protein, Pre-S1 protein, and Pre-S2 protein.
33 . The aqueous pharmaceutical composition according to claim 32 , wherein the HBsAg antigen comprises 75-90% by weight S protein, 2-8% by weight Pre-S1 protein, and 5-15% by weight Pre-S2 protein.
34 . The aqueous pharmaceutical composition according to claim 30 , wherein the ratio of the HBsAg antigen to the aluminum present in the adjuvant is 60:500.
35 . The aqueous pharmaceutical composition according to claim 30 , wherein the ratio of the HBsAg antigen to the aluminum present in the adjuvant is 40:500.
36 . The aqueous pharmaceutical composition according to claim 30 , wherein the ratio of the HBsAg antigen to the aluminum present in the adjuvant is 20:500.
37 . A method of inducing a Th1 cell response in a mammal, said method comprising administering aqueous pharmaceutical composition of claim 30 .
38 . A method of treating Hepatitis B in a subject, said method comprising administering a therapeutically effective amount of the aqueous pharmaceutical composition of claim 30 to the subject.
39 . The method of claim 38 , wherein an additional Hepatitis B treatment is administered to the subject prior to, concurrently with, or after administration of the aqueous pharmaceutical composition to the subject.
40 . The method of claim 39 , wherein the additional Hepatitis B treatment is a nucleoside inhibitor or a pegylated interferon alpha.
41 . The method of claim 39 , 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, an interferon, an immune modulator or an siRNA.