Abstract: The present application provides immunotherapies for Hepatitis B virus infections. Provided herein are genetically modified arenaviral vectors suitable as vaccines for prevention and treatment of Hepatitis B virus infections. Also provided herein are pharmaceutical compositions and methods for the treatment of Hepatitis B virus infections. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of treating Hepatitis B virus infection.

Abstract: This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

Abstract: Disclosed are nucleic acid oligomers for amplifying one or more selected regions of HCV nucleic acid. Also disclosed are methods for specific amplification and characterization of HCV nucleic acid using the disclosed oligomers, as well as corresponding reaction mixtures and kits.

Abstract: This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

Abstract: The invention provides fibronectin type III (Fn3)-based binding molecules that bind to a specific target antigen. The invention further provides bispecific Fn3-based binding molecules that bind to two or more targets simultaneously. The Fn3-based binding molecules of the invention can also be linked together to form multispecific Fn3-based binding molecules, and/or can be conjugated to a non-Fn3 moiety, such as, Human Serum Albumin (HSA), for improved half life and stability. The invention also provides methods for generating, screening and using Fn3-based binding molecules in a variety of therapeutic and diagnostic applications.

Abstract: Materials and methods useful for generating highly mannosylated pseudotyped lentiviral vector particles comprising a Vpx protein are provided.

Abstract: The construction of a chimeric Pestivirus by the identification of selected regions in the 3?NTR of the viral RNA genome is described where additional RNA sequences can be stably inserted. These sequence insertions in the viral RNA genome were stable in replication and capable of forming infectious, RNase resistant virus particles. This chimeric Pestivirus with a 3?NTR insertion can be utilized as a quality control material in analytical assays for RNA targets, including external, internal controls, quantitative standards in PCR and NAT nucleic acid assays.

Abstract: The present disclosure provides a method of treating a human patient in need thereof with immune reconstitution therapy by administering a therapeutically effective amount of therapeutic T cell population selected and/or expanded from a mobilised blood sample or a mobilised apheresis sample, wherein selection is on the basis of a steady state marker and/or an activation marker optionally followed by expansion, or expansion is in the presence of antigen, such as a viral antigen. It also extends to methods of generating said therapeutic T cell populations and the product obtainable therefrom.

Abstract: Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.

Abstract: The present invention provides a nucleic acid comprises a 5? untranslated region, an NS3 protein coding region, an NS4A protein coding region, an NS4B protein coding region, an NS5A protein coding region, an NS5B protein coding region, and a 3? untranslated region of a hepatitis C virus genome, wherein the nucleic acid has nucleotide substitutions causing one or more amino acid substitutions selected from the group consisting of M(1205)K, F(1548)L, C(1615)W, T(1652)N, A(2196)T, A(2218)S, H(2223)Q, Q(2281)R, K(2520)N, and G(2374)S, as defined using the amino acid sequence shown in SEQ ID NO: 6 in the Sequence Listing as a reference sequence, in the NS3 protein coding region, the NS5A protein coding region, or the NS5B protein coding region.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2 transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analysis.

Abstract: The present invention relates to compositions and methods for the prevention and treatment of infectious diseases. In particular, the invention relates to stimulating an immune response in a subject to prevent or treat diseases by administering a DNA vaccine encoding regulatory elements derived from the caprine arthritis encephalitis goat lentivirus genome and at least one immunogenic molecule to the subject. The immunogenic molecules used with the present invention may be capable of stimulating an immune response to any infectious disease causing agent. In particular, the invention is useful for stimulating an immune response to infectious diseases caused by lentiviruses. For instance, the present invention is directed to a DNA vaccine for immunization against HIV.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.

Abstract: The present invention 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 include are methods of inducing an immune response in a subject and vaccinating a subject by administering such compositions.

Abstract: The invention relates to immunogenic compositions useful as HCV vaccines. Provided are HCV mosaic polypeptide and nucleic acid compositions which provide higher levels of T-cell epitope coverage while minimizing the occurrence of unnatural and rare epitopes compared to natural HCV polypeptides and consensus HCV sequences.

Abstract: Disclosed herein are isolated nucleic acids, compositions of isolated nucleic acids, 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 hepatitis B core antigen (HBcAg) protein and a heterologous protein antigen. In some embodiments, an isolated nucleic acid encoding hepatitis B core antigen (HBcAg) protein and a heterologous protein antigen is disclosed. Also disclosed herein are methods of administering the composition or isolated nucleic acid to generate an immune response, where HBcAg acts as adjuvant to improve the immune response to the heterologous protein. In certain embodiments, the HBcAg is as a stork or heron hepatitis antigen.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated form of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: This invention relates to cholesterol-sequestering agents and methods of using cholesterol-sequestering agents to treat or prevent infection. The compositions of the invention can be used in vitro or in vivo to decrease the load of a microorganism in a biological sample. Methods of generating an immune response against a microorganism are also included.

Abstract: PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

Abstract: The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

Abstract: The present invention relates to a composition for preventing or treating liver diseases, which contains, as an active ingredient, any one or more of a homogeneous cell line derived from the cambium of Panax ginseng, including wild ginseng or ginseng, a lysate thereof, an extract thereof and a culture medium thereof. The homogeneous cell line according to the present invention, a lysate thereof, an extract thereof and a culture medium thereof have minimized side effects compared to existing agents for treating liver diseases, and thus are safe for the human body. Also, they can increase the levels of s-antibody (HBsAb) and e-antibody (HBeAb) against hepatitis virus and inhibit the proliferation of hepatitis virus, and thus they are useful for the prevention and treatment of liver diseases. In addition, they have the effect of lowering the levels of liver injury, and thus are useful as a functional food for improving liver function.

Abstract: The invention relates to compositions and methods that employ OX40 (CD134), a TNFR superfamily protein, agonists. The invention includes among other things administering an OX40 agonist alone or in combination with a viral antigen, or live or attenuated virus, to treat a viral infection, or for vaccination or immunization.

Abstract: Methods and compositions for eliciting an immune response to an antigen are disclosed. In certain aspects, these methods concern eliciting an immune response in a subject by administering to the mucosa of the subject a composition comprising a virus-like particle (“VLP”) and Murabutide.

Abstract: A biodegradable and thermosensitive poly(organophosphazene) with a functional group, a preparation method thereof, and a use thereof for delivery of bioactive substances are provided.

Abstract: The present invention relates generally to the fields of immunology and vaccine technology. More specifically, the invention relates to mucosal administration via aerosol spray to avians of immunogenic and vaccine compositions, including those comprising recombinant human adenovirus vectors for delivery of genes encoding avian immunogens or antigens, such as genes encoding avian influenza virus. The invention also provides methods and apparatus for use in such administration.

Abstract: The present invention provides a pharmaceutical composition with an adjuvant based on an apathogenic virus, together with an antigen. The adjuvant has a natural or through genetical engineering no, reduced or altered expression of an endogenous interferon antagonist or endogenous immune suppressor.

Abstract: The present invention provides vectors that contain and express in vivo or in vitro CDV polypeptides or antigens that elicit an immune response in animal against CDV, compositions comprising said vectors and/or CDV polypeptides, and methods of vaccination against CDV. The invention further provides methods for inducing an immunogenic or protective response against CDV and other canine virus, as well as methods for preventing or treating CDV and other canine virus or disease state(s) caused by CDV and other canine virus.

Abstract: The present invention provides a polynucleotide adjuvant (PICKCa) composition and methods of use in eliciting an immune response, in particular a mucosal immune response. The polynucleotide adjuvant comprises of a polyriboinosinic-polyribocytidylic acid (PIC), at least one antibiotic and at least one positive ion. The present invention also provides an immunogenic composition comprising the polynucleotide adjuvant composition together with other immunogenic compositions such as an antigen (e.g., as in a vaccine) selected from viral, bacterial, fungal, parasitic and/or cancer antigens. The present invention further contemplates methods of use of such adjuvant compositions, particularly in eliciting an immune response, in particular a mucosal immune response to an antigenic compound.

Abstract: Improved (safer and more effective) methods of therapy using TNF-R agonists, e.g., CD40 agonists are provided. These methods provide for the addition of an amount of a type 1 interferon and/or a TLR agonist that is effective to prevent or reduce the toxicity (liver toxicity) that may otherwise result in some patients of the TNF-R agonist is used as a monotherapy (without the type 1 interferon and/r TLR agonist).

Abstract: This invention relates to the use of a CCR4 antagonist as an adjuvant, in particular in an immunogenic composition comprising an antigen which elicits an immune response against a pathogen or tumour.

Abstract: This invention provides a dry powder composition for poultry vaccination via inhalation comprising an effective amount of a poultry vaccine agent, and a supporting amount of carriers for said poultry vaccine agent, said carriers comprising a combination of a reducing or non-reducing sugar and a biocompatible polymer, said dry powder composition being in the form of particles having an average particle size from 2 to 30 ?m and a particle size polydispersity from 1.1 to 4.0. This invention also relates to a method for producing said dry powder compositions and a system for vaccination of poultry by inhalation.

Abstract: The invention provides, inter alia, immunogenic compositions that comprise (a) a first antigen, (b) at least first and second adjuvants, wherein the first adjuvant comprises microparticles and wherein the second adjuvant comprises an imidazoquinoline compound, and (c) a pharmaceutically acceptable excipient, which compositions elicits an immune response when administered to a vertebrate subject. The invention also provides methods of producing immunogenic compositions and methods for using immunogenic compositions (e.g., for treatment), among other benefits.

Abstract: The invention relates to the field of biology. In particular, it relates to multi-epitope nucleic acid and peptide vaccines and methods of designing such vaccines to provide increased immunogenicity.

Abstract: A dry composition for use in therapy or diagnosis, obtainable by drying an aqueous composition comprising a protein and one or more displacement buffers, wherein the pH of the aqueous composition is such that the protein is stable, wherein the or each displacement buffer has a pKa that is at least 1 unit greater or less than the pH of the aqueous composition, and wherein the aqueous composition is substantially free of a conventional buffer having a pKa that is within one pH unit of the pH of the aqueous composition.

Abstract: The invention is within the field of immunology and microbiology, more specifically the field of virology and is related to immunotherapy and prophylaxis of hepatitis and autoimmune diseases. The composition useful for these purposes is disclosed, including the methods of making and using said composition.

Abstract: The present invention relates to a novel isolated avian hepatitis E virus having a nucleotide sequence set forth in SEQ ID NO:1 or its complementary strand. The invention further concerns immunogenic compositions comprising this new virus or recombinant products such as the nucleic acid and vaccines that protect an avian or mammalian species from viral infection or hepatitis-splenomegaly syndrome caused by the hepatitis E virus. Also included in the scope of the invention is a method for propagating, inactivating or attenuating a hepatitis E virus comprising inoculating an embryonated chicken egg with a live, pathogenic hepatitis E virus and recovering the virus or serially passing the pathogenic virus through additional embryonated chicken eggs until the virus is rendered inactivated or attenuated.

Abstract: The present invention provides recombinant nucleic acid molecules, expression cassettes, and vectors useful for expression of polypeptides, including heterologous polypeptides, such as antigens, in bacteria. Some of the recombinant nucleic acid molecules, expression cassettes and vectors comprise codon-optimized sequences encoding the polypeptides and/or signal peptides. Some of the recombinant nucleic acid molecules, expression cassettes, and expression vectors comprise sequences encoding non-Listerial and/or non-secA1 signal peptides for secretion of the polypeptides. The invention also provides bacteria comprising the nucleic acid molecules, expression cassettes, and expression vectors, as well as compositions such as vaccines comprising the bacteria. Methods of making and using the bacteria, recombinant nucleic acid molecules, and expression cassettes are also provided.

Abstract: A composition for treating or preventing virus-induced infections is described, along with a process of producing the composition and methods of the composition's use. The composition comprises viral pathogen-infected cell or tissue, or malignantly or immunologically aberrant cells or tissues which has been reduced and/or denatured. The preferred composition is administered across a mucosal surface of an animal suffering or about suffer from infection. The composition is administered as preventive or therapeutic vaccine.

Abstract: Disclosed herein are sterile-filtered lyophilized nanoparticle compositions which contain at least one biodegradable polymer, at least one surfactant, at least one cryoprotective agent and at least one antigen. Also disclosed are methods of making and using such compositions and kits supplying such compositions.

Abstract: The invention is in general directed to methods and compositions for preventing or treating infections by viruses involved in persistent and/or latent infections. The methods and compositions are directed toward the prevention and treatment of infections caused by viruses such as, for example, herpesviruses, retroviruses, hepatitis viruses, and papillomaviruses, including, for example, cytomegalovirus.

Abstract: Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural viral proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural genes of a second flavivirus strain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

Abstract: Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (?-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

Abstract: The present invention relates to a pharmaceutical composition containing an mRNA that is stabilised by sequence modifications in the translated region and is optimised for the translation. The pharmaceutical composition according to the invention is particularly suitable as an inoculating agent as well as a therapeutic agent for tissue regeneration. In addition a process is described for determining sequence modifications that serve for the stabilisation and translation optimisation of mRNA.

Abstract: The present invention discloses recombinant adenovirus and methods of administration of the virus to a host inorder to elicit an immune response against various pathogens in the host. Specifically, a vaccination method to enhance immunity of the host to the pathogen is disclosed herein. Such a method comprises recombinant adenoviruses expressing viral antigens, where the recombinant adenoviruses are derived from different serotypes or subtypes. Alternatively, the adenoviruses in such a method can also be constructed by modifying the backbone of one of the adenoviruses (e.g. the knob, shaft or fiber regions) so that it is of a serotype that is different from the corresponding region(s) in the backbone of the other recombinant adenovirus.

Abstract: The present inventors developed three 4a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and all of or part of NS2 were replaced by the corresponding genes of the genotype 4a reference strain ED43. The 4a/2a junction in NS2 was placed after the first transmembrane domain (a), in the cytoplasmic part (?) or at the NS2/NS3 cleavage site (y). Following transfection of Huh7.5 cells with RNA transcripts, infectious viruses were produced in the ED43/JFH1-? and -y cultures only. Compared to the 2a control virus, production of infectious viruses was significantly delayed. However, in subsequent passages efficient spread of infection and high HCV RNA titers were obtained. Infectivity titers were approximately 10-fold lower than for the 2a control virus. Sequence analysis of recovered 4a/2a recombinants from 3 serial passages and subsequent reverse genetic studies revealed a vital dependence on a mutation in the NS2 4a part. ED43/JFH1-? further depended on a second NS2 mutation.

Abstract: The present invention features methods and compositions related to chitosan antigen depots, and chitosan cytokine depots, and the use of depot compositions in treating and preventing diseases.

Abstract: The invention provides an immunogenic composition comprising at least one antigen in association with micropar-tides, wherein the microparticles are in the same size range as viruses. In addition the invention also provides vaccine compositions and methods of eliciting immune responses in a subject.

Abstract: The present invention provides a vaccine composition comprising an effective amount of antigen or a nucleic acid encoding antigen, encapsulated in polymeric particles, wherein said polymeric particles comprises nanoparticles, microparticles or combinations thereof, wherein surprisingly the nanoparticle induces cellular response and the microparticle induces humoral response. The invention further provides a method of inducing cellular and/or humoral immune response.