Abstract: Immunogenic compositions comprising an immunogenic polypeptide and a pharmaceutically acceptable vehicle are described. The immunogenic polypeptide comprises the amino acid sequence 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). The immunogenic polypeptide can be coupled to a pharmaceutically acceptable carrier, such as a diphtheria toxoid.

Abstract: The present invention relates to new genomic nucleotide sequences and amino acid sequences corresponding to the coding region of these genomes. The invention relates to new HCV types and subtypes sequences which are different from the known HCV types and subtypes sequences. More particularly, the present invention relates to new HCV type 7 sequences, new HCV type 9 sequences, new HCV type 10 and new HCV type 11 sequences. Also, the present invention relates to new HCV type 1 sequences of subtypes 1d, 1e, 1f and 1g; new HCV type 2 sequences of subtypes 2e, 2f, 2g, 2h, 2i, 2k and 2l; new HCV type 3 sequences of subtype 3g, new HCV type 4 sequences of subtypes 4k, 4l and 4m; a process for preparing them, and their use for diagnosis, prophylaxis and therapy. More particularly, the present invention provides new type-specific sequences of the Core, the E1 and the NS5 regions of new HCV types 7, 9, 10 and 11, as well as of new variants (subtypes) of HCV types 1, 2, 3 and 4.

Abstract: A process is disclosed for preparation of a immunogenic peptide mixture in a single synthesis. The peptide mixture collectively represents the in vivo variability seen in immunogenic epitopes from a pathogen. The mixture is termed a hypervariable epitope construct (HEC). Immunization with a HEC evokes broadly reactive immunity against divergent strains of a pathogen upon which the HEC is based.

Abstract: The invention relates to Hepatitis C virus epitopes which are specific in relation to CD4+ T lymphocytes, in addition to vaccinations which contain said epitopes.

Abstract: This invention provides an isolated strain of Hepatitis B virus designated Human Hepatitis B Virus Surface Antigen-‘S’-133 Oon Strain (Methionine to Threonine) which constituent viral genome is deposited under Accession Nos. P97121501, P97121502 and P97121503 with the European Collection of Cell Culture on 15th Dec. 1997. This invention also provides an isolated nucleic acid encoding a polypeptide which is a mutant major surface antigen of a strain of hepatitis B virus, such polypeptide having an amino acid sequence which differs from the amino acid sequence of a major surface antigen of a wild type hepatitis B virus in that the amino acid at position number 133 of such polypeptide is a threonine rather than a methionine. This invention also provides an isolated nucleic acid which encodes a peptide, wherein the peptide is encoded by a nucleic acid molecule comprising nucleotides 527 through 595 of SEQ. I.D. No. 1 and the purified peptide.

Abstract: Immunogenic polypeptides comprising hepatitis C virus (HCV) immunogens are described. The HCV immunogen comprises the amino acid sequence Xaa-Thr-Xaa-Val-Thr-Gly-Gly-Xaa-Ala-Ala-Arg-Thr-Thr-Xaa-Gly-Xaa-Xaa-Ser-Leu-P he-Xaa-Xaa-Gly-Xaa-Ser-Gln-Xaa-Ile-Gln-Leu-Ile (SEQ ID NO:8). The immunogenic polypeptide can be coupled to a bacterial toxoid, such as a diphtheria toxoid.

Abstract: Viral proteins derived from an enterically transmitted non-A/non-B viral hepatitis agent (HEV) are disclosed. In one embodiment, the protein is immunologically reactive with antibodies present in individuals infected with the viral hepatitis agent. This protein is useful in a diagnostic method for detecting infection by the enterically transmitted agent. Specific epitopes have been identified that are reactive with sera of individual infected with different strains of HEV. Also disclosed are DNA probes derived from a cloned sequence of the viral agent. These probes are useful for identifying and sequencing the entire viral agent and for assaying the presence of the viral agent in an infected sample, by using probe-specific amplification of virus-derived DNA fragments.

Abstract: The present invention discloses nucleic acid sequence which encodes infectious hepatitis C virus of strain HC-J6CH, gentotype 2a, and the use of the sequence, and polypeptides encoded by all or part of the sequence, 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: 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: The nucleotide and deduced amino acid sequences of cDNAs encoding the envelope 1 genes and core genes of isolates of hepatitis C virus (HCV) are disclosed. The invention relates to the oligonucleotides, peptides and recombinant envelope 1 and core proteins derived from these sequences and their use in diagnostic methods and vaccines.

Abstract: We isolated and characterized a new surface mutant of the hepatitis B virus surface antigen (HBsAg). The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab.

Abstract: Antigenic epitopes of hepatitis C virus (HCV) and mosaic HCV polypeptides useful as reagents in assays for the diagnosis or monitoring of HCV in a biological sample. The antigenic epitopes and mosaic polypeptides are also useful for the construction of immunogenic pharmaceutical compositions, such as vaccines. The mosaic polypeptides are artificial composite proteins constructed from diagnostically relevant antigenic regions derived from different HCV proteins. Preferably, the mosaic polypeptides contain antigenic epitopes from the core protein, NS3 protein, and NS4 protein. The preferred mosaic polypeptides optionally contain an additional antigenic epitope from either the NS4 protein or the NS5a protein or both.

Abstract: Novel hepatitis C virus (HCV) polypetides are provided which are not encoded by the standard HCV open reading frame. These alternate reading frame polypeptides are useful, inter alia, in vaccine compositions, in diagnosing HCV infection, and as therapeutic targets.

Abstract: The present invention relates to the general field of recombinant protein expression, purification of recombinant proteins, diagnosis of HCV infection, prophylactic treatment against HCV infection and to the prognosing/monitoring of the clinical efficiency of treatment of an individual with chronic hepatitis, or the prognosing/monitoring of the natural disease. In particular, the present invention relates to the use of yeast, i.e. Hansenula or Saccharomyces glycosylation minus strains, for the efficient expression of HCV envelope proteins that are core-glycosylated, purification methods for these proteins, and the use in various applications, such as the use in diagnosis, prophylaxis or therapy of HCV envelope proteins purified according to the present invention.

Abstract: This invention provides an isolated strain of Hepatitis B virus designated Human Hepatitis B Virus Surface Antigen-'?-145 Singapore Strain (Glycine to Arginine) which constituent viral genome is deposited under Accession Nos. P97121504, P97121505 and P97121506 with the European Collection of Cell Culture on 15th Dec. 1997. This invention also provides an isolated nucleic acid encoding a polypeptide which is a mutant major surface antigen of a strain of hepatitis B virus, such polypeptide having an amino acid sequence which differs from the amino acid sequence of a major surface antigen of a wild type hepatitis B virus in that the amino acid at position number 145 of such polypeptide is an arginine rather than a glycine, and the purified peptide. This invention further provides an isolated nucleic acid which encodes a peptide, wherein the peptide is encoded by a nucleic acid molecule comprising nucleotides 527 through 595 of SEQ. ID. No. 1, and the purified peptide.

Abstract: Compositions of HBsAg particles having biologically active molecules contained in the particles, and methods of their use, e.g. in stimulating enhanced immune responses, are described. Antigenic peptides contained in HBsAg particles were found to produce a CTL response where none was elicited by the peptide alone. Encapsulation of immunostimulating molecules, such as cytokines, greatly enhanced the CTL response evoked by the HBsAg particles themselves.

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: Polypeptides comprising a mutant non-structural Hepatitis C virus useful in diagnostic and/or immunogenic compositions are disclosed, in which the mutant is an N-terminal mutation that functionally disrupt the catalytic domain of NS3. Polynucleotides encoding these polypeptides, host cells transformed with polynucleotides and methods of using the polypeptides and polynucleotides are also disclosed.

Abstract: The invention concerns a structural peptide, identified by antibodies directed against a polypeptide, comprising the 2-45 amino acid sequence of the N-terminal end of the Core or nucleocapsid (p21) protein of the hepatitis C virus (HCV), excluding any protein or peptide compound comprising or consisting of the N-terminal end. The invention is characterized in that it comprises a tertiary structure consisting of at least a first peptide fragment having a secondary structure in ? helix, a second peptide fragment having secondary structure in ? helix and a third peptide bond fragment linking the two ? helices, these two ? helices being substantially perpendicular to each other in space. This peptide can be used for detecting antibodies directed against the p21 protein of HCV, for detecting all of part of the RNA of HCV and for preparing a diagnostic, prophylactic or therapeutic composition for detecting, preventing or treating an HCV infection.

Abstract: The invention provides compositions and processes for the production of ordered and repetitive antigen or antigenic determinant arrays. The compositions of the invention are useful for the production of vaccines for the prevention of infectious diseases, the treatment of allergies and the treatment of cancers. Various embodiments of the invention provide for a core particle that is coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions.

Abstract: Novel combined vaccine composition preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a V2V antigen, a HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3D-MPL and QS21.

Abstract: The present invention relates to recombinant hepatitis C virus (HCV)-derived nucleic acids and to stable rapidly growing cell clones derived from human hepatoma Huh-7 cell line and supporting high titer replication of said recombinant HCV nucleic acids. The subgenomic HCV replicons and cell clones of the instant invention represent the in vitro system of choice for studies of HCV propagation, anti-viral drug screening, and vaccine development.

Abstract: The invention relates to HBV antigen-containing compositions that are useful in treating or preventing HBV infection. The content of the compositions can vary, as described herein, but the compositions comprise a stress protein, or a portion (e.g., a fragment) or derivative thereof, and an HBV antigen.

Abstract: The immune response to a DNA immunogen in a mammal can be enhanced by administration of a chemokine or a polynucleotide encoding the chemokine. This method can be used, for example, to immunize or vaccinate a mammal against an infectious disease or a tumor.

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: A vaccine formulation for the treatment or prophylaxis of hepatitis, especially hepatitis, especially hepatitis B, infections is provided comprising the hepatitis antigen and a suitable carrier such as alum in combination with 3-O-deacylated monophosphoryl lipid. A combination vaccines including the vaccine formulation are also described.

Abstract: The present invention provides particles for the presentation of haptens for the purpose of eliciting an immune response. The amino acid sequences of the monomers which make up the particles are derived from duck hepatitis B virus core protein. The particles may also deliver nucleic acids. The nucleic acids may be delivered for the purpose of enhancing an immune response, or for other purposes such as gene therapy.

Abstract: Newly elucidated sequences of hepatitis C virus type 4 and type 5 are described, together with those of a newly discovered type 6. Unique type-specific sequences in the NS4, NS5 and core regions enable HCV detection and genotyping into types 1 to 6. Antigenic peptides and immunoassays are described.

Abstract: GB virus C (GBV-C or hepatitis G virus) is a recently described flavivirus that frequently leads to chronic viremia in humans. Although associated with acute post-transfusion hepatitis, it is not clear if GBV-C is pathogenic for humans. A full-length cDNA was constructed from the plasma of a person with chronic GBV-C viremia. Peripheral blood mononuclear cells (PBMCs) transfected with full-length RNA transcripts from this GBV-C clone resulted in viral replication, demonstrating an isolated infectious GBV-C nucleic acid molecule. In addition to composition involving an isolated infectious GBV-C nucleic acid molecule, the present invention concerns methods of inhibiting and treating HIV infections.

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 subject invention relates to methods for the simultaneous detection of Hepatitis C Virus (HCV) antigens as well as antibodies produced in response to HCV antigens. Furthermore, the subject invention allows one to detect antigens in the early, acute stage of infection, even prior to the development of antibodies, thereby allowing for early detection of infected blood and blood products, thus improving the safety of the blood supply.

Abstract: Multimer peptides (e.g. 30- to 45-mer peptides) derived from hepatitis C virus envelope proteins reacting with the majority of anti-HCV antibodies present in patient sera are described. The usage of the latter peptides to diagnose, and to vaccinate against, an infection with hepatitis C virus is also disclosed.

Abstract: The present invention features Ad6 vectors and a nucleic acid encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide containing an inactive NS5B RNA-dependent RNA polymerase region. The nucleic acid is particularly useful as a component of an adenovector or DNA plasmid vaccine providing a broad range of antigens for generating an HCV specific cell mediated immune (CMI) response against HCV.

Abstract: This invention relates to hepatitis B virus (“HBV”) core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them.

Abstract: The present invention relates to an adjuvant derived from human lymphocytes. The adjuvant can be used in combination with traditional vaccines or cancer immunotherapy, to enhance the response of the patient's immune system to the vaccine or other immunotherapeutic agent. The adjuvant is derived from the supernatant collected from cultured activated lymphocytes.

Abstract: Formulation of vaccine antigens, containing as main components: a-) one or several DNA expressing one or several proteins in the immunized individuals and b-) a viral antigen, in appropriate proportions. The novelty of the invention is given by the enhancing effect of at least one component on the immune response generated against the other one.

Abstract: The invention relates to open reading frame 2 (ORF-2) proteins of a swine hepatitis E virus and the use of these proteins as an antigen in diagnostic immunoassays and/or as immunogen or vaccine to protect against infection by hepatitis E.

Abstract: The present invention provides particles for the presentation of haptens for the purpose of eliciting an immune response. The amino acid sequences of the monomers which make up the particles are derived from duck hepatitis B virus core protein. The particles may also deliver nucleic acids. The nucleic acids may be delivered for the purpose of enhancing an immune response, or for other purposes such as gene therapy.

Abstract: Disclosed are compositions and methods for preferentially binding hK2 over PSA.

Abstract: The present invention relates to materials and methods for treatment of hepatitis C. More closely, the invention relates to human monoclonal antibodies against HCV E1 antigen, to a reagent comprising such antibodies, and to vaccine compositions comprising such antibodies. Futhermore, the invention relates to a method of treating or preventing HCV infection by administration of a vaccine composition comprising the monoclonal antibodies of te invention.

Abstract: The present invention is related to the method for obtaining aggregated antigenic structures that are capable of enhancing an immune response to aggregate antigens administered systemically and/or mucosally generating powerful immune response and to the chemical structures resulting from the application of said method, to the formulations obtained from such structures and their use. The method describes the obtention of novel aggregate antigenic structures by using aggregating, delipidating or oxidating agents or compounds enabling the release of lipids from the particles and their heterogeneous aggregation, wherein aggregates with particle sizes of between 30 and 500 nm are subsequently selected by means of a molecular exclusion process. The aggregation state can also be provoket inside the yeast by changing incubation conditions.

Abstract: New methods and reagents for vaccination are described which generate a CD8 T cell immune response against malarial and other antigens such as viral and tumour antigens. Novel vaccination regimes are described which employ a priming composition and a boosting composition, the boosting composition comprising a non-replicating or replication-impaired pox virus vector carrying at least one CD8 T cell epitope which is also present in the priming composition.

Abstract: The present invention relates generally to an immunogenic complex comprising a charged organic carrier and a charged antigen and, more particularly, a negatively charged organic carrier and a positively charged antigen, wherein the charged antigen is a polyprotein of Hepatitis C Virus (HCV), particularly the core protein of HCV, or a fragment thereof, or a fusion protein comprising the polyprotein or a fragment thereof. The complexes of the present invention are useful, inter alia, in vaccine compositions as therapeutic and/or prophylactic agents for facilitating the induction of immune responses, and in particular a cytotoxic T-lymphocyte response, in the treatment of a disease condition which results from an HCV infection.

Abstract: HCV immunoassays comprising an NS3/4a conformational epitope and a multiple epitope fusion antigen are provided, as well as immunoassay solid supports for use with the immunoassays.

Abstract: The present invention relates to HCV proteins in which cysteine residues are reversibly protected during purification. Eventually, this purification procedure results in HCV proteins with biological activity and a native-like protein conformation, which present corresponding epitopes. The present invention pertains also to drug screening methods using these HCV proteins, and diagnostic and therapeutic applications, such as vaccines and drugs.

Abstract: Novel combination of preservatives (methyl and propyl parabens, benzyl alcohol, and 2-phenoxyethanol) were found to pass antimicrobial testing according to USP, BP, and EP. The new preservatives were put into vaccines using L-histidine as a buffer to keep pH at 7.0. HPLC methods were developed to analyze these preservatives and their degradation products.

Abstract: A strain of hepatitis E virus from Pakistan (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, is disclosed. The invention relates to the expression of the whole structural region of SAR-55, designated open reading frame 2 (ORF-2), in a eukaryotic expression system. The expressed protein is capable of forming HEV virus-like particles which can serve as an antigen in diagnostic immunoassays and as an immunogen or vaccine to protect against infection by hepatitis E.

Abstract: This invention provides an isolated strain of Hepatitis B virus designated Human Hepatitis B Virus Surface Antigen-‘S’-133 Oon Strain (Methionine to Threonine) which constituent viral genome is deposited under Accession Nos. P97121501, P97121502 and P97121503 with the European Collection of Cell Culture on 15th December 1997. This invention also provides an isolated nucleic acid encoding a polypeptide which is a mutant major surface antigen of a strain of hepatitis B virus, such polypeptide having an amino acid sequence which differs from the amino acid sequence of a major surface antigen of a wild type hepatitis B virus in that the amino acid at position number 133 of such polypeptide is a threonine rather than a methionine. This invention also provides an isolated nucleic acid which encodes a peptide, wherein the peptide is encoded by a nucleic acid molecule comprising nucleotides 527 through 595 of SEQ. I.D. No. 1 and the purified peptide.

Abstract: A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (HBc) is disclosed that is engineered for both enhanced stability of self-assembled particles and the display of an immunogenic epitope. The display of the immunogenic epitope is displayed in the immunogenic loop of HBc, whereas the enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near the carboxy-terminus of the chimer molecule. Methods of making and using the chimers are also disclosed.

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.