Abstract: Disclosed are compositions, including vaccines, and methods for vaccinating an animal against hepatitis C virus (HCV) and for treating or preventing hepatitis C viral infection in an animal. The invention includes a variety of novel HCV fusion proteins that can be used directly as a vaccine or in conjunction with a yeast-based vaccine vehicle to elicit an immune response against HCV in an animal. The invention also includes the use of the HCV fusion gene and protein described herein in any diagnostic or therapeutic protocol for the detection and/or treatment or prevention of HCV infection.

Abstract: The anti-viral vaccine of the present invention is produced in transgenic plants and then administered through standard vaccine introduction method or through the consumption of the edible portion of those plants. A DNA sequence encoding for the expression of a surface antigen of a viral pathogen is isolated and ligated to a promoter which can regulate the production of the surface antigen in a transgenic plant. This gene is then transferred to plant cells using a procedure that results in its integration into the plant genome, such as through the use of an Agrobacterium tumenfaciens plasmid vector system. Preferably, the foreign gene is expressed in an portion of the plant that is edible by humans or animals. In a preferred procedure, the vaccine is administered through the consumption of the edible plant as food, preferably in the form of a fruit or vegetable juice which can be taken orally.

Abstract: The invention relates to sequences of a novel variant of the Hepatitis B surface antigen (HBsAg) and to methods for detecting, in patient samples, nucleic acids, antigens and antibodies directed against the same.

Abstract: GB virus C (GBV-C or hepatitis G virus) is a flavivirus that frequently leads to chronic viremia in humans. The invention provides compositions and methods involving an anti-GBV-C antibody or other GBV-C binding agent, or a GBV-C antigen, for inhibiting and treating HIV infections.

Abstract: Disclosed herein is the discovery of a novel hepatitis C virus (HCV) isolated from a human patient. Embodiments of the invention include HCV peptides, nucleic acids encoding said HCV peptides, antibodies directed to said peptides, compositions containing said nucleic acids and peptides, as well as, methods of making and using the aforementioned compositions including, but not limited to, diagnostics and medicaments for the treatment and prevention of HCV infection.

Abstract: The present invention relates to hepatitis virus core proteins and nucleic acids. In particular, the present invention provides compositions and methods comprising recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.

Abstract: The invention relates to recombinantly or synthetically produced HCV E1 envelope proteins or parts thereof comprising disulfides between specific cysteine residues. The invention further relates to viral-like particles and compositions comprising said HCV E1 envelope proteins or parts thereof as well as to methods using said HCV E1 envelope proteins or parts thereof, and to kits comprising said HCV E1 envelope proteins or parts thereof.

Abstract: The present invention relates generally to viral variants exhibiting reduced sensitivity to particular agents and/or reduced interactivity with immunological reagents. More particularly, the present invention is directed to hepatitis B virus (HBV) variants exhibiting complete or partial resistance to nucleoside analogs and/or reduced interactivity with antibodies to viral surface components including reduced sensitivity to these antibodies. The present invention further contemplates assays for detecting such viral variants, which assays are useful in monitoring anti-viral therapeutic regimens and in developing new or modified vaccines directed against viral agents and in particular HBV variants. The present invention also contemplates the use of the viral variants to screen for agents capable of inhibiting infection, replication and/or release of the virus.

Abstract: The present invention relates to a polynucleic acid composition comprising or consisting of at least one polynucleic acid containing 8 or more contiguous nucleotides corresponding to a nucleotide sequence from the region spanning positions 417 to 957 of the Core/E1 region of HCV type 3; and/or the region spanning positions 4664 to 4730 of the NS3 region of HCV type 3; and/or the region spanning positions 4892 to 5292 of the NS3/4 region of HCV type 3; and/or the region spanning positions 8023 to 8235 of the NS5 region of the BR36 subgroup of HCV type 3a; and/or the coding region of HCV type 4a starting at nucleotide 379 in the core region; and/or the coding region of HCV type 4; and/or the coding region of HCV type 5, with said nucleotide numbering being with respect to the numbering of HCV nucleic acids as shown in Table 1, and with said polynucleic acids containing at least one nucleotide difference with known HCV type 1, and/or HCV type 2 genomes in the above-indicated regions, or the complement thereof.

Abstract: The invention relates to novel peptide compositions. In particular, the invention relates to a peptide composition comprising at least two peptides which are selected from among the following peptides: a peptide A having at least the amino acid sequence of SEQ ID No1, a peptide B having at least the amino acid sequence of SEQ ID No45, a peptide C having at least the amino acid sequence of SEQ ID No127, a peptide D having at least the amino acid sequence of SEQ. ID No174. The inventive compositions can be used, in particular, in the preparation of active pharmaceutical compositions against the hepatitis C virus.

Abstract: The present invention relates to hepatitis virus core proteins and nucleic acids. In particular, the present invention provides compositions and methods comprising recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.

Abstract: Embodiments of the invention disclosed herein relate to methods and compositions for bypassing the involvement of CD4+ cells when generating antibody and MHC class I-restricted immune responses, controlling the nature and magnitude of the response, and promoting effective immunologic intervention in viral pathogenesis. More specifically, embodiments relate to immunogenic compositions for vaccination particularly therapeutic vaccination, against HIV and other microbial pathogens that impact functioning of the immune system, their nature, and the order, timing, and route of administration by which they are effectively used.

Abstract: Described is a method for isolating Hepatitis C Virus peptides (HPs) which have a binding capacity to a MHC/HLA molecule or a complex comprising said HCV-peptide and said MHC/HLA molecule characterized by the following steps: —providing a pool of HCV-peptide, said pool containing HCV-peptides which bind to said MHC/HLA molecule and HCV-peptides which do not bind to said MHC/HLA molecule, —contacting said MHC/HLA molecule with said pool of HCV-peptides whereby a HCV-peptide which has a binding capacity to said MHC/HLA molecule binds to said MHC/HLA molecule and a complex comprising said HCV-peptide and said MHC/HLA molecule is formed, —detecting and optionally separating said complex from the HCV-peptide which do not bind to said MHC/HLA molecule and optionally isolating and characterizing the HCV-peptide from said complex.

Abstract: The present invention is related to the branch of medicine, particularly to the new formulations of vaccine antigens. The technical objective pursued with the present invention is, precisely, the development of formulations that are able to enhance the immune response to mucosally administered antigens, minimising the number of compounds in the formulation and generating strong mucosal and systemic responses through a synergic interaction between the antigens in the formulation. These formulations enable: a) to broaden the spectrum of the anti-hepatitis B immune response, containing as main compounds HBsAg and HBcAg, b) to enhance the response against HBsAg with a viral nucleocapsid c) to generate combined vaccines through the mucosal route with HBsAg as a central antigen. Stabilizers and preservatives can be introduced. The formulations of this invention can be applied in the pharmaceutical industry as human or veterinary vaccine formulations.

Abstract: Disclosed are compositions, including vaccines, and methods for vaccinating an animal against hepatitis C virus (HCV) and for treating or preventing hepatitis C viral infection in an animal. The invention includes a variety of novel HCV fusion proteins that can be used directly as a vaccine or in conjunction with a yeast-based vaccine vehicle to elicit an immune response against HCV in an animal. The invention also includes the use of the HCV fusion gene and protein described herein in any diagnostic or therapeutic protocol for the detection and/or treatment or prevention of HCV infection.

Abstract: The subject invention relates to a novel hepatitis B surface antigen mutant and methods of detecting this mutant, and/or antibodies thereto, in patient samples. In particular, the mutant contains a substitution of amino acid threonine for the amino acid alanine at position 123 in the amino acid sequence of the hepatitis B surface antigen (HBsAg) protein.

Abstract: Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV envelope, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens.

Abstract: This invention relates to a mutant E. coli heat-labile enterotoxin (LT) subunit A that can be used as an adjuvant. This subunit A mutant contains an amino acid substitution at a position corresponding to position 61 of a wild-type LT. An LT containing this mutated subunit A exhibits reduced toxicity compared to its wild type counterpart.

Abstract: A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid (HBc) protein is disclosed that contains an immunogen for inducing the production of antibodies to the influenza M2 protein. An immunogenic influenza sequence in two to four copies is preferably expressed at or near the N-terminus or in the HBc immunogenic loop sequence. The HBc chimer preferably contains an influenza-specific T cell epitope and is preferably engineered for both enhanced stability of self-assembled particles and enhanced yield of those chimeric particles. Methods of making and using the chimers are also disclosed.

Abstract: The present invention provides a cell line capable producing infectious hepatitis C virus 1a (HCV 1a) particles in culture. Disclosed are compositions and methods for an HCV 1a (clone H77) transfected immortal human hepatocyte (IHH) capable of generating infectious HCV 1a virus particles in culture. Also disclosed are methods of using the cell line, or HCV 1a virus particles derived from said cell line, to screen for potential therapeutic agents which interfere with HCV 1a virus propagation to treat hepatic disease.

Abstract: The invention concerns nucleic acid molecules derived from novel hepatitis D virus strains or isolates constituting genotypes different from known I, II and III genotypes, their fragments, corresponding proteins and their uses as diagnostic reagents. The invention also concerns a method for sensitive diagnosis of the hepatitis D virus (or delta hepatitis virus) and a method for epidemiologic monitoring of HDV-related infections.

Abstract: A method of treating chronic hepatitis B is disclosed that comprises administering a T cell-stimulating amount of a vaccine to a patient. The vaccine comprises an immunogenic amount of chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid (core) protein (HBc) that is engineered for both enhanced stability of self-assembled particles and the substantial absence of nucleic acid binding by those particles. The chimeric protein molecule can include one or more immunogenic epitopes peptide-bonded to one or more of the N-terminus, the immunogenic loop or the C-terminus of HBc. The enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near one or both of the amino-terminus and carboxy-terminus of the chimer molecule.

Abstract: The present invention relates to isolation of a novel Hepatitis C virus, more particularly, the present invention relates to a viral class Hepatitis C, polypeptides, polynucleotide, vaccine and antibodies derived there from.

Abstract: Disclosed is a peptide derived from hepatitis C virus comprising an HLA-binding motif in its sequence and being recognized by an antibody detected in a patient with hepatitis C virus (HCV) infection. The peptide of the present invention is useful in diagnosing hepatitis C virus, treating hepatitis C, and predicting the prognosis of hepatitis C.

Abstract: Provided are an isolated peptide having the amino acid sequence DLMGYIPAV (SEQ ID NO: 1), an isolated HCV core polypeptide comprising an L?A substitution at amino acid position 139, an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2, and a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence of SEQ ID NO:1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. Further provided are methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

Abstract: A method for enhancing an immune response to a nucleic acid vaccine comprising administering to an animal a nucleic acid construct encoding a fusion protein comprising a processing component and an antigenic polypeptide of interest wherein said processing component provides heterogeneous processing of the antigenic polypeptide when the nucleic acid construct is expressed in a host cell and a resulting enhancement of the immune response. The processing component is derived from an N-terminal portion of PORF2 of Hepatitis E virus.

Abstract: The present invention relates to hepatitis virus core proteins and nucleic acids. In particular, the present invention provides compositions and methods comprising recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.

Abstract: The invention relates to a method of detecting HCV infection in a biological sample, the method comprising providing an immunoassay solid support, comprising an HCV anti-core antibody, an antigen comprising an HCV NS3/4a epitope, and an HCV multiple epitope fusion antigen, that can detect both HCV antigens and antibodies present in a sample. The invention also includes polynucleotides encoding multiple epitope fusion antigens for use in the assay, recombinant vectors and host cells comprising such polynucleotides, and methods of producing the multiple epitope fusion antigens.

Abstract: The current invention relates to vectors and methods for efficient expression of HCV envelope proteins in eukaryotic cells. More particularly said vectors comprise the coding sequence for an avian lysozyme signal peptide or a functional equivalent thereof joined to a HCV envelope protein or a part thereof. Said avian lysozyme signal peptide is efficiently removed when the protein comprising said avian lysozyme signal peptide joined to a HCV envelope protein or a part thereof is expressed in a eukaryotic cell. Suitable eukaryotic cells include yeast cells such as Saccharomyces or Hansenula cells.

Abstract: The present invention relates to a method for detection and/or genetic analysis of HBV in a biological sample, comprising hybridizing the polynucleic acids of the sample with a combination of at least two nucleotide probes, with said combination hybridizing specifically to a mutant target sequence chosen from the HBV RT pol gene region and/or to a mutant target sequence chosen from the HBV preCore region and/or to a mutant target sequence chosen from the HBsAg region of HBV and/or to a HBV genotype-specific target sequence, with said target sequences being chosen from FIG.

Abstract: Aspects of the present invention relate to the discovery of a novel hepatitis C virus (HCV) isolate. Embodiments include HCV peptides, nucleic acids encoding said HCV peptides, antibodies directed to said peptides, compositions containing said nucleic acids and peptides, as well as methods of making and using the aforementioned compositions including, but not limited to, diagnostics and medicaments for the treatment and prevention of HCV infection.

Abstract: The present application provides GB virus C sequences (GBV-C or hepatitis G virus) and methods of using the sequences.

Abstract: The invention provides a method of activating hepatitis C virus (HCV)-specific T cells, including CD4+ and CD8+ T cells. HCV-specific T cells are activated using fusion proteins comprising HCV NS3, NS4, NS5a, and NS5b polypeptides, polynucleotides encoding such fusion proteins, or polypeptide or polynucleotide compositions containing the individual components of these fusions. The method can be used in model systems to develop HCV-specific immunogenic compositions, as well as to immunize a mammal against HCV.

Abstract: The invention relates to hepatitis C virus epitopes which are CD4+ T-lymphocyte specific, and to vaccines containing these epitopes.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: A diagnostic reagent for hepatitis C virus infection obtained by sensitizing a solid phase with HCV antigen and a conjugated antigen prepared by chemical bonding of HCV antigen and a carrier protein, and a method of diagnosing hepatitis C virus infection, which comprises adding the diagnostic reagent for hepatitis C virus infection to a sample, and measuring the degree of agglutination of carrier particles as the solid phase. The diagnostic reagent and the method of diagnosis enable many samples to be measured with higher sensitivity and rapidity.

Abstract: Fusion proteins comprising an immunogenic polypeptide are disclosed. The immunogenic polypeptide consists of the amino acid sequence motif Xaa-Thr-Xaa-Val-Thr-Gly-Gly-Xaa-Ala-Ala-Arg-Thr-Thr-Xaa-Gly-Xaa-Xaa-Ser-Leu-Phe-Xaa-Xaa-Gly-Xaa-Ser-Gln-Xaa-Ile-Gln-Leu-Ile (SEQ ID NO:8). Also disclosed are immunogenic compositions comprising a pharmaceutically acceptable carrier and the fusion protein.

Abstract: Compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans are disclosed. More particularly, vaccine compositions comprising ribavirin and an antigen, preferably an antigen that has an epitope present in Hepatitis C virus (HCV), are disclosed for use in treating and preventing disease, preferably HCV infection.

Abstract: The current invention relates to HCV envelope proteins or parts thereof which are the product of expression in eukaryotic cells. More particularly said HCV envelope proteins are characterized in that on average up to 80% of their N-glycosylation sites are core-glycosylated. Of these N-glycosylated sites more than 70% are glycosylated with an oligomannose having a structure defined by Man(8 to 10)-GlcNAc(2). Furthermore, the ratio of the oligomannose with structure Man(7)-GlcNAc(2) over the oligomannose with structure Man(8)-GlcNAc(2) is less than or equal to 0.45. Less than 10% of the oligomannoses is terminated with an ?1,3 linked mannose. The HCV envelope proteins of the invention are particularly suited for diagnostic, prophylactic and therapeutic purposes. A suitable eukaryotic cell for production of the HCV envelope proteins of the invention is a Hansenula cell.

Abstract: A diagnostic reagent for hepatitis C virus infection obtained by sensitizing a solid phase with HCV antigen and a conjugated antigen prepared by chemical bonding of HCV antigen and a carrier protein, and a method of diagnosing hepatitis C virus infection, which comprises adding the diagnostic reagent for hepatitis C virus infection to a sample, and measuring the degree of agglutination of carrier particles as the solid phase. The diagnostic reagent and the method of diagnosis enable many samples to be measured with higher sensitivity and rapidity.

Abstract: The subject invention relates to a novel hepatitis B surface antigen mutant and methods of detecting this mutant, and/or antibodies thereto, in patient samples. In particular, the mutant contains a substitution of amino acid threonine for the amino acid alanine at position 123 in the amino acid sequence of the hepatitis B surface antigen (HBsAg) protein.

Abstract: The invention provides compositions containing HCV epitopes, which are recognized by cytotoxic T lymphocytes. Such polypeptides are used in prophylactic vaccines, immunotherapies, and assays to monitor the progress or success of immune interventions. The compositions are optimized to elicit an immune response in a genetically-diverse population of individuals.

Abstract: The present invention discloses nucleic acid sequences which encode infectious hepatitis C viruses and the use of these sequences, and polypeptides encoded by all or part of these sequences, in the development of vaccines and diagnostics for HCV and in the development of screening assays for the identification of antiviral agents for HCV.

Abstract: The present invention relates to a polynucleic acid composition comprising or consisting of at least one polynucleic acid containing 8 or more contiguous nucleotides corresponding to a nucleotide sequence from the region spanning positions 417 to 957 of the Core/E1 region of HCV type 3; and/or the region spanning positions 4664 to 4730 of the NS3 region of HCV type 3; and/or the region spanning positions 4892 to 5292 of the NS3/4 region of HCV type 3; and/or the region spanning positions 8023 to 8235 of the NS5 region of the BR36 subgroup of HCV type 3a; and/or the coding region of HCV type 4a starting at nucleotide 379 in the core region; and/or the coding region of HCV type 4; and/or the coding region of HCV type 5, with said nucleotide numbering being with respect to the numbering of HCV nucleic acids as shown in Table 1, and with said polynucleic acids containing at least one nucleotide difference with known HCV type 1, and/or HCV type 2 genomes in the above-indicated regions, or the complement thereof.

Abstract: The present invention relates to a polynucleic acid composition comprising or consisting of at least one polynucleic acid containing 8 or more contiguous nucleotides corresponding to a nucleotide sequence from the region spanning positions 417 to 957 of the Core/E1 region of HCV type 3; and/or the region spanning positions 4664 to 4730 of the NS3 region of HCV type 3; and/or the region spanning positions 4892 to 5292 of the NS3/4 region of HCV type 3; and/or the region spanning positions 8 023 to 8 235 of the NS5 region of the BR36 subgroup of HCV type 3a; and/or the coding region of HCV type 4a starting at nucleotide 379 in the core region; and/or the coding region of HCV type 4; and/or the coding region of HCV type 5, with said nucleotide numbering being with respect to the numbering of HCV nucleic acids as shown in Table 1, and with said polynucleic acids containing at least one nucleotide difference with known HCV type 1, and/or HCV type 2 genomes in the above-indicated regions, or the complement thereof.

Abstract: An isolated polypeptide comprises the amino acid sequence of SEQ ID NO: 11, wherein the expression of said polypeptide is significant lower specifically in human livers with hepatitis compared with that in human health livers. The detection of said polypeptide expression in human liver can be used as a diagnosis for human hepatitis.

Abstract: An HCV antigen/antibody/antigen assay is provided. The assay employs an isolated first antigen from a region of the HCV polyprotein, and an HCV multiple epitope fusion antigen that includes an epitope from the same region of the polyprotein as the first antigen. Both the first antigen and the multiple epitope fusion antigen bind antibodies present in an HCV-infected sample.

Abstract: The invention relates to post-transfusional non-A non-B hepatitis viral polypeptide, DNA sequences encoding such viral polypeptide, expression vectors containing such DNA sequences, and hosts transformed by such expression vectors. The invention also relates to the use of such polypeptides in diagnostic assays and vaccine formulations.

Abstract: The present invention relates to hepatitis virus core proteins and nucleic acids. In particular, the present invention provides compositions and methods comprising recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.

Abstract: The subject invention relates to a novel hepatitis B surface antigen mutant and methods of detecting this mutant, and/or antibodies thereto, in patient samples. In particular, the mutant contains a substitution of amino acid threonine for the amino acid alanine at position 123 in the amino acid sequence of the hepatitis B surface antigen (HBsAg) protein.