Disclosed herein are methods, compositions, and kits useful to enhance an immune response against an antigen and to improve vaccine efficacy. The disclosed methods, compositions, and kits may be utilized to improve vaccine immunogenicity and enhance immune protection following subsequent antigen challenges. In some embodiments, the methods include co-administering a blocker of the IFN-I pathway with an antigen that is used as part of a vaccine, such as a viral vaccine.

A vaccine delivery method is presented that includes a composition including as one component a slurry matrix that is a liquid at room temperature and a gel at physiological pH, physiological salt concentrations and/or physiological temperatures and as a second component one or more antigens. Also included are methods of inducing an immune response in a subject and vaccinating a subject by administering such compositions.

A vaccine delivery method is presented that includes a composition including as one component a slurry matrix that is a liquid at room temperature and a gel at physiological pH, physiological salt concentrations and/or physiological temperatures and as a second component one or more antigens. Also included are methods of inducing an immune response in a subject and vaccinating a subject by administering such compositions.

A pharmaceutical composition comprising at least two peptides of from 15 to 60 amino acids in length, selected from peptides comprising a sequence of at least 15 contiguous amino acids of one of the sequences shown in SEQ ID NOs: 1 to 4 or of a sequence having at least 80% identity to one of the sequences shown in SEQ ID NOs: to 4, wherein each peptide comprises at least one CD8+ T-cell epitope and/or at least one CD4+ T-cell epitope and wherein each peptide elicits a response in peripheral blood mononuclear cells (PBMC) from at least one chronically infected HBV individual in an 10 in vitroassay.

The present invention relates to peptides and their ability to identify and bind to T cells specific for HBV-infected hepa-tocytes. In an first aspect of the invention, there is provided a peptide comprising an amino sequence selected from the group consisting of STLPETAVVRR, STLPETAVVR, STLPETTVVRR, STLPETTVIRR, STPPETTVVRR, STLPETTVVGR and STIPETTVVRR, wherein the peptide is derived from Hepatitis B virus core169 and is capable of binding HLA-A*1101 and when bound to HLA-A*1101 s capable of identifying T cells specific for Hepatitis B virus. In a second aspect of the invention, there is provided A T cell expressing a T cell receptor (TCR) molecule, wherein the TCR molecule comprises an amino acid sequence selected from the group comprising: CASGDSNSPLHF, CASSGGQIVYEQYF, CSARGGRGGDYTF and CASSQDWTEAFF, the T cell receptor is able to bind to a pep-tide according to the first aspect of the invention.

There is provided a method of treating chronic hepatitis B infection (CHB) and/or chronic hepatitis D infection (CHD) in a human, comprising the steps of: a) administering to the human a composition comprising an antisense oligonucleotide (ASO) 10 to 30 nucleosides in length, targeted to a HBV nucleic acid (an HBV ASO); b) administering to the human a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); c) administering to the human a composition comprising a Modified Vaccinia Virus Ankara (MVA) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); and d) administering to the human a composition comprising a recombinant hepatitis B surface antigen (HBs), recombinant hepatitis B virus core antigen (HBc) and an adjuvant.

Provided herein are engineered hepatitis B virus (HBV) molecular vaccine constructs. Vaccine constructs can also include ligand-inducible engineered gene switch systems for modulating expression of heterologous genes, such as a cytokines, in host cells.

The present disclosure provides compositions and methods useful for inducing a The 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%.

Chimeric genes, compositions of chimeric genes, and compositions of polypeptides that are useful for the generation, enhancement, or improvement of an immune response to a target antigen. Some embodiments of the compositions include chimeric genes encoding hepatitis D antigen (HDAg) protein in combination with one or more self-cleavage 2A polypeptides and a preS1 polypeptide. In certain embodiments the self-cleavage polypeptide is P2A.

Chimeric genes, compositions of chimeric genes, and compositions of polypeptides that are useful for the generation, enhancement, or improvement of an immune response to a target antigen. Some embodiments of the compositions include chimeric genes encoding hepatitis D antigen (HDAg) protein in combination with one or more self-cleavage 2A polypeptides and a preS1 polypeptide. In certain embodiments the self-cleavage polypeptide is P2A.