Abstract: The present invention discloses a method for assessing the capacity of a substance to treat or prevent hepadnavirus infection. A reporter virus carrying genetic information for a first fragment of a recombinase and a reporter cell expressing a second fragment of the recombinase are used. When the reporter virus infects the reporter cell, the two fragments of the recombinase associate and excise a stop cassette that is flanked by two recombination sites and blocks the expression of a reporter gene. Accordingly, the present invention relates to a method of assessing the capacity of a substance to treat or prevent hepadnavirus infection, a hepadnavirus comprising a nucleic acid encoding a first fragment of a recombinase and a mammalian hepatocyte or hepatoma cell comprising a nucleic acid encoding a second fragment of a recombinase and a nucleic acid comprising a stop cassette flanked by two recombination sites fused to a reporter gene.

Abstract: The present invention provides methods for the treatment of a subject having a Hepatitis B virus (HBV) infection, e.g., a chronic HBV infection, using a combination of an RNAi agent that targets HBV and an HBV vaccine. It is disclosed a RNAi agent and an HBV vaccine for use in treatment of HBV infection, comprising sequentially administering to the subject having an HBV infection: a) an RNAi agent that inhibits expression of at least three HBV transcripts, wherein the RNAi agent forms a double stranded region; b) a protein-based vaccine comprising a first HBV core antigen (HBcAg) polypeptide, and a first HBV surface antigen (HBsAg) polypeptide; and c) a nucleic acid-based vaccine comprising an expression vector construct encoding a second HBcAg polypeptide, and/or a second HBsAg polypeptide, wherein the second HBcAg polypeptide, and/or the second HBsAg polypeptide, shares at least one epitope with at least one of the first HBcAg polypeptide, and/or the first HBsAg polypeptide.

Abstract: The present invention relates to a porcine sodium taurocholate cotransporter polypeptide (NTCP) mutein, which has been modified at sequence positions 157-167 with the human sequence. This NTCP mutein renders a host cell and a transgenic animal susceptible for an infection with hepatitis B virus (HBV) and/or hepatitis D virus (HDV). The present invention further relates to a nucleic acid and a vector comprising the NTCP mutein of the invention. Also presented are methods for producing cells and transgenic animals, which are susceptible to HBV and/or HDV as well as uses of the NTCP mutein screening for compounds or rendering a cell susceptible for an infection with HBV and/or HDV. Additionally provided is a method for identifying a compound, which is useful in the prevention and/or treatment of HBV and/or HDV infection.

Abstract: The present invention relates to an improved recombinant vaccination vector for the treatment or vaccination against hepatitis B virus (HBV) as well as pharmaceutical compositions or vaccines comprising said recombinant vaccination vector. The present invention also relates to a recombinant vaccination vector for use in a method of vaccination against HBV, as well as kits comprising a vaccine comprising the recombinant vaccination vector.

Abstract: The present invention relates to a polypeptide comprising (a) a first set of six complementarity determining regions (CDRs) configured to bind a first antigen; and (b) (ba) a second set of six CDRs configured to bind a second antigen; or (bb) a ligand capable of binding to a second antigen; wherein (i) said first antigen is selected from Hepatitis B virus (HBV) small surface antigen; HBV medium surface antigen; and HBV large surface antigen; and (ii) said second antigen is selected from surface antigens presented by immune effector cells such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Also provided are compositions for use in a method of treating or preventing HBV infection and/or a condition caused by said HBV infection, said condition caused by said HBV infection being selected from liver cirrhosis and hepatocellular carcinoma.

Abstract: The present invention relates to a binding molecule comprising at least three binding specificities, wherein (a) the first specificity is for a Hepatitis B virus (HBV) surface antigen selected from HBV small surface antigen, HBV medium surface antigen and HBV large surface antigen; (b) (i) the second and third specificity are for CD3 and CD28, respectively; or (ii) the second and third specificity are selected from specificities for CD16, CD56, NKp30, NKp46, 4-1BB and NKG2D; and (c) each binding specificity is provided by one or more binding sites, each binding site being independently provided by (i) a set of six complementarity determining regions (CDRs), wherein said set of six CDRs consists of a first set of three CDRs and a second set of three CDRs, wherein said first and said second set is each comprised in an immunoglobulin domain; or (ii) a set of three CDRs, wherein said set of three CDRs is comprised in an immunoglobulin domain.

Abstract: The present invention discloses a method for assessing the capacity of a substance to treat or prevent hepadnavirus infection. A reporter virus carrying genetic information for a first fragment of a recombinase and a reporter cell expressing a second fragment of the recombinase are used. When the reporter virus infects the reporter cell, the two fragments of the recombinase associate and excise a stop cassette that is flanked by two recombination sites and blocks the expression of a reporter gene. Accordingly, the present invention relates to a method of assessing the capacity of a substance to treat or prevent hepadnavirus infection, a hepadnavirus comprising a nucleic acid encoding a first fragment of a recombinase and a mammalian hepatocyte or hepatoma cell comprising a nucleic acid encoding a second fragment of a recombinase and a nucleic acid comprising a stop cassette flanked by two recombination sites fused to a reporter gene.

Abstract: The present invention provides methods for the treatment of a subject having a Hepatitis B virus (HBV) infection, e.g., a chronic HBV infection, using a combination of an RNAi agent that targets HBV and an HBV vaccine. It is disclosed a RNAi agent and an HBV vaccine for use in treatment of HBV infection, comprising sequentially administering to the subject having an HBV infection: a) an RNAi agent that inhibits expression of at least three HBV transcripts, wherein the RNAi agent forms a double stranded region; b) a protein-based vaccine comprising a first HBV core antigen (HBcAg) polypeptide, and a first HBV surface antigen (HBsAg) polypeptide; and c) a nucleic acid-based vaccine comprising an expression vector construct encoding a second HBcAg polypeptide, and/or a second HBsAg polypeptide, wherein the second HBcAg polypeptide, and/or the second HBsAg polypeptide, shares at least one epitope with at least one of the first HBcAg polypeptide, and/or the first HBsAg polypeptide.

Abstract: The present invention relates to compounds and compositions for use in methods of treating and/or preventing conditions, disorders or diseases that are mediated or caused by a virus.

Abstract: In a first aspect, the present invention relates to the use of a TLR 9 agonist and/or a TLR 4 agonist in a prophylactic or therapeutic vaccine. According to the present vaccination strategy, the TLR 9 agonist and/or TLR 4 agonist is adapted or designed for use as a multiplying jump agent to enhance numbers and functionality of CD8 T cells in a prime-jump vaccination strategy for jump T cell expansion. In particular, the TLR 9 agonist and/or TLR 4 agonist is used as a component to be administered after priming of the individual to be vaccinated. The vaccination strategy is particularly useful against acute and chronic infections with intracellular pathogens or for anti-tumor vaccination. In another aspect, the present invention relates to a kit of part containing a prime agent and a multiplying jump agent according to the present invention.

Abstract: The present invention relates to an improved recombinant vaccination vector for the treatment or vaccination against hepatitis B virus (HBV) as well as pharmaceutical compositions or vaccines comprising said recombinant vaccination vector. The present invention also relates to a recombinant vaccination vector for use in a method of vaccination against HBV, as well as kits comprising a vaccine comprising the recombinant vaccination vector.

Abstract: The present invention relates to a polypeptide comprising (a) a first set of six complementarity determining regions (CDRs) configured to bind a first antigen; and (b) (ba) a second set of six CDRs configured to bind a second antigen; or (bb) a ligand capable of binding to a second antigen; wherein (i) said first antigen is selected from Hepatitis B virus (HBV) small surface antigen; HBV medium surface antigen; and HBV large surface antigen; and (ii) said second antigen is selected from surface antigens presented by immune effector cells such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Also provided are compositions for use in a method of treating or preventing HBV infection and/or a condition caused by said HBV infection, said condition caused by said HBV infection being selected from liver cirrhosis and hepatocellular carcinoma.

Abstract: The present invention relates to a polypeptide comprising (a) a first set of six complementarity determining regions (CDRs) configured to bind a first antigen; and (b) (ba) a second set of six CDRs configured to bind a second antigen; or (bb) a ligand capable of binding to a second antigen; wherein (i) said first antigen is selected from Hepatitis B virus (HBV) small surface antigen; HBV medium surface antigen; and HBV large surface antigen; and (ii) said second antigen is selected from surface antigens presented by immune effector cells such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Also provided are compositions for use in a method of treating or preventing HBV infection and/or a condition caused by said HBV infection, said condition caused by said HBV infection being selected from liver cirrhosis and hepatocellular carcinoma.

Abstract: The present invention relates to compounds and compositions for use in methods of treating and/or preventing conditions, disorders or diseases that are mediated or caused by a virus.

Abstract: The present invention relates to a binding molecule comprising at least three binding specificities, wherein (a) the first specificity is for a Hepatitis B virus (HBV) surface antigen selected from HBV small surface antigen, HBV medium surface antigen and HBV large surface antigen; (b) (i) the second and third specificity are for CD3 and CD28, respectively; or (ii) the second and third specificity are selected from specificities for CD16, CD56, NKp30, NKp46, 4-1BB and NKG2D; and (c) each binding specificity is provided by one or more binding sites, each binding site being independently provided by (i) a set of six complementarity determining regions (CDRs), wherein said set of six CDRs consists of a first set of three CDRs and a second set of three CDRs, wherein said first and said second set is each comprised in an immunoglobulin domain; or (ii) a set of three CDRs, wherein said set of three CDRs is comprised in an immunoglobulin domain.

Abstract: The present invention relates to glypican-3-specific T-cell receptors. The present invention further relates to soluble TCR constructs, chimeric TCRs, bi-specific antibodies, nucleic acids, expression constructs and cells comprising said TCRs or TCR constructs. The present invention further relates to the use of the TCR or the soluble TCR constructs or chimeric TCRs or bi-specific antibodies as a medicament, preferably in the detection, diagnosis, prognosis, prevention and/or treatment of liver cancer, in particular hepatocellular carcinoma, or other cancers expressing GPC3. The present invention further relates to methods of detecting, diagnosing, prognosing, preventing and/or treating liver cancer, in particular hepatocellular carcinoma, or other cancers expressing GPC3. The present invention further relates to peptides comprising glypican-3 epitope(s) and respective nucleic acids encoding them, antibodies and compositions as well as their use as (peptide) vaccines.

Abstract: The present invention relates to a polypeptide comprising (a) a first set of six complementarity determining regions (CDRs) configured to bind a first antigen; and (b) (ba) a second set of six CDRs configured to bind a second antigen; or (bb) a ligand capable of binding to a second antigen; wherein (i) said first antigen is selected from Hepatitis B virus (HBV) small surface antigen; HBV medium surface antigen; and HBV large surface antigen; and (ii) said second antigen is selected from surface antigens presented by immune effector cells such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Also provided are compositions for use in a method of treating or preventing HBV infection and/or a condition caused by said HBV infection, said condition caused by said HBV infection being selected from liver cirrhosis and hepatocellular carcinoma.

Abstract: In a first aspect, the present invention relates to the use of a TLR 9 agonist and/or a TLR 4 agonist in a prophylactic or therapeutic vaccine. According to the present vaccination strategy, the TLR 9 agonist and/or TLR 4 agonist is adapted or designed for use as a multiplying jump agent to enhance numbers and functionality of CD8 T cells in a prime-jump vaccination strategy for jump T cell expansion. In particular, the TLR 9 agonist and/or TLR 4 agonist is used as a component to be administered after priming of the individual to be vaccinated. The vaccination strategy is particularly useful against acute and chronic infections with intracellular pathogens or for anti-tumor vaccination. In another aspect, the present invention relates to a kit of part containing a prime agent and a multiplying jump agent according to the present invention.

Abstract: Methods and compositions for efficient, hepatocyte-specific delivery and expression of heterologous genes, both in-vitro and in-vivo, using hepadnaviral vectors are provided. Methods for expressing a heterologous gene in hepatocytes are provided involving: providing replication defective hepadnavirus particles at a titre level competent to infect hepatocytes, wherein a region of the preS/S-gene of the hepadnavirus genome has been replaced with the heterologous gene such that expression of the heterologous gene is regulated by regulatory sequences of the preS/S-gene; and infecting hepatocytes with the hepadnavirus such that the heterologous gene is delivered into the hepatocytes and expressed in the hepatocytes. Methods for treating a subject with a hepatic disorder (e.g., hepatitis infection) are also provided. Replication defective hepadnavirus particles, and pharmaceutical compositions thereof, are also provided.