Abstract: The present invention pertains to a Salmonella microorganism having an attenuating mutation which disrupts the expression of a gene located within the Spi2 pathogenicity island, and an auxotrophic mutation. The microorganism therefore has a double mutation which helps prevent reactivity of the microorganism while maintaining the effectiveness of the microorganism to elicit an immune response. The present invention also pertains to vaccine compositions and methods for treating and preventing a Salmonella infection in a patient.

Abstract: The present invention is directed to a method of inducing an immune response against a hepatitis B antigen (e.g., an antigen from a hepatitis B virus) in a mammal, which comprises administering to the mammal a priming composition (e.g., a DNA plasmid), comprising a source of one or more epitopes of the hepatitis B target antigen; and a boosting composition, comprising a source of one or more eptiopes of the hepatitis B target antigen (e.g., a non-replication or replication-impaired poxvirus such as MVA), wherein at least one epitope of the boosting composition is identical to an epitope of the priming composition. The present invention also is directed to a method of inducing an immune response against a hepatitis B antigen (e.g., an antigen from a hepatitis B virus) in a mammal, which comprises administering to the mammal a priming composition (e.g., a DNA plasmid), comprising a source of one or more epitopes of the hepatitis B target antigen.

Abstract: The invention provides novel vaccination strategies based on a prime-boost vaccination regiment. The inventors have determined improved ways of boosting an immune response in a patient previously primed or exposed to a plurality of epitopes. The improved method requires the epitopes in the boosting phase to be administered individually, i.e. held on separate peptide constructs.

Abstract: The present invention provides compositions for making a medicament and methods for the administration of a vaccine compositions for protection against human rotaviral disease without significant reactogenicity. Human x rhesus reassortant rotavirus compositions were made which when administered during the first 7 to about 10 days of life, provided a composition which was non-reactogenic followed by booster immunizations at 16 to 18 weeks or 14 to 20 weeks, up to 1 year of age. The immune response induced by the initial neonatal administration of the live rotavirus vaccine composition protects the infant from the reactogenicity of the composition when administered as a second vaccine dose at or after 2 months of age. Administration of the immunogenic composition also is expected to ablate or significantly diminish the increase in the excess of intussusception observed 3 to 7 days following administration of the initial dose of rotavirus vaccine at about 2 to 4 months.

Abstract: The present invention relates to monoparamunity inducers based on paramunizing viruses or viral components of a myxomavirus strain from rabbits with typically generalizing disease, to a method for the production thereof and to the use thereof as medicaments for the regulatory optimization of the paramunizing activities for the prophylaxis and therapy of various dysfunctions in humans and animals.

Abstract: Embodiments of the present invention generally relate to novel methods for the treatment and/or prevention of neurological symptoms caused by an avian reovirus, enteric reovirus strain (ERS), and associated characteristics. Other embodiments generally comprise and immunogenic composition or vaccine comprising an ERS for the treatment and/or prevention of neurological symptoms.

Abstract: The invention relates to the recombinant production of proteins as well as VLPs which are suitable as a vaccine for therapeutic and prophylactic vaccination. The invention also relates to processes for the production and purification of recombinant papilloma virus proteins and fusion proteins.

Abstract: The present invention provides for a novel oil-in-water (O/W) emulsion, with increased stability in the presence of bacterial or viral suspensions, especially those concentrated and non-purified or weakly purified. The emulsion of the present invention can act as vehicle for the delivery of a pharmaceutical composition comprising at least one immunogen and, in particular, an immunogen selected from the group comprising an inactivated pathogen, an attenuated pathogen, a subunit, a recombinant expression vector, and a plasmid or combinations thereof.

Abstract: The present invention provides a recombinant, attenuated infectious laryngotracheitis virus comprising the infectious laryngotracheitis viral genome which contains a deletion in the glycoprotein gG gene. This attenuated virus is useful as a vaccine against infectious laryngotracheitis virus. The present invention also provides a recombinant, attenuated infectious laryngotracheitis virus comprising the infectious laryngotracheitis viral genome which contains a deletion in the US2 gene, UL47-like gene, ORF4 gene or glycoprotein g60 gene. The present invention also provides a method for distinguishing chickens or other poultry vaccinated with a recombinant infectious laryngotracheitis virus which produces no glycoprotein gG from those infected with a naturally-occurring infectious laryngotracheitis virus.

Abstract: The invention provides recombinant flavivirus vaccines that can be used in the prevention and treatment of flavivirus infection. The vaccines of the invention contain recombinant flaviviruses including attenuating mutations.

Abstract: This invention provides liquid rotavirus formulations that are suitable for oral administration to human infants. In particular, the invention provides pharmaceutical compositions and vaccines, comprising a rotavirus antigen, a sugar and a carboxylate, wherein said formulation has a pH of between pH 5.0 and pH 8.0 and comprises no phosphate or less than 5 mM phosphate. The invention also provides methods of preparing said rotavirus formulations and use thereof in the prevention or treatment or rotavirus associated diseases in humans.

Abstract: The present invention is directed to compositions and methods for the delivery of interferon polypeptides. The invention provides recombinant viral and non-viral vectors for the selective expression of interferon polypeptides in particular cell or tissue types. The invention further provides pharmaceutically acceptable formulations of such vectors for administration to mammalian subjects. The invention further provides methods of treatment of diseases in mammalian organisms through the delivery of recombinant vectors selectively expressing interferon polypeptides.

Abstract: The present invention relates to the use of a pneumovirus NS1 protein and/or NS2 protein or a nucleic acid encoding pneumovirus NS1 protein and/or NS2 protein for the preparation of a pharmaceutical formulation for reducing the immune response mediated by interferon (IFN). The invention further relates to recombinant pneumoviruses, in particular respiratory syncytial viruses (RSV), having an increased, reduced, or lacking a resistance to the interferon (IFN) mediated immune response, recombinant viruses having an increased resistance to the interferon (IFN) mediated immune response, and the use of the viruses in pharmaceutical applications, e.g. as vaccines.

Abstract: Use for novel chemokine-binding protein designated A41L, and chemokine-binding fragments thereof, for the treatment of conditions such as inflammation. The A41L protein binds to chemokines in the CXC group.

Abstract: The cold-adapted master strain A/Ann Arbor/6/60 7PI (H2N2) and progenitor wild type E2(3) viral strains have been deposited and their genomic sequences identified. Seven nucleotide differences were found between the sequences identified herein and the previously published sequences for cold-adapted A/Ann Arbor/6/60 genes. The cold-adapted live influenza virus of the present invention can be reassorted with a variety of epidemic wild type influenza viruses and used to produce vaccines to prophylactically and therapeutically treat influenza.

Abstract: Transposon linker insertion mutagenesis of a full-length infectious clone of the highly pathogenic classical swine fever virus (CSFV) isolate Brescia (pBIC) was used to identify genetic determinants of CSFV virulence and host range. A virus mutant, RB-C22 (RB-C22v), possessing a 19-residue tag insertion at the carboxyl end of E1 was constructed. RB-C22v and the parental virus pBIC (pBICv) exhibited similar growth characteristics on primary porcine macrophage cell cultures although RB-C22v produced significantly smaller plaques on SK6 cell cultures. In vivo, RB-C22v was markedly attenuated in swine. In contrast with pBIC infection, where mortality was 100%, all RB-C22v-infected pigs survived infection remaining clinically normal. Additionally, chimeras of the Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Chimeras 138.8v and 337.14v, chimeras containing the E2 glycoprotein of CS and chimeric virus 319.

Abstract: An inactivated influenza virus preparation is described which comprises a haemagglutinin antigen stabilized in the absence of thiomersal, or at low levels of thiomersal, wherein the haemagglutinin is detectable by a SRD assay. The influenza virus preparation may comprise a micelle modifying excipient, for example ?-tocopherol or a derivative thereof in a sufficient amount to stabilize the haemagglutinin.

Abstract: The invention provides modified virus Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing human immunodeficiency virus (HIV) env, gag, and pol genes.

Abstract: Agents and methods for enhancing recombinant virus transduction in the bladder epithelium are described. A first method involves contacting the luminal surface of the bladder with a composition comprising a transduction enhancing agent and an oncolytic virus. Alternatively, the luminal surface of the bladder can be contacted first with a pretreatment composition comprising a transduction enhancing agent and, subsequently, with a composition comprising an oncolytic virus. Bladder treatment compositions comprising a transduction enhancing agent and an oncolytic virus are also described.

Abstract: Methods and compositions for the optimization of production of influenza viruses suitable as influenza vaccines are provided.

Abstract: Chimeric parainfluenza viruses (PIVs) are provided that incorporate a PIV vector genome or antigenome modified to encode a chimeric glycoprotein incorporating one or more heterologous antigenic domains, fragments, or epitopes of a second, antigenically distinct HPIV. These chimeric viruses are infectious and attenuated in humans and other mammals and are useful in vaccine formulations for eliciting an immune responses against one or more PIVs, and, optionally against respiratory syncytial virus (RSV). Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a HPIV vector genome or antigenome combined or integrated with one or more heterologous genome segment(s) encoding one or more antigenic determinant(s) of a heterologous PIV to encode a chimeric glycoprotein.

Abstract: The present invention provides new Pestiviral RNA genomes (replicons) that are able to replicate, and can be packaged into infectious viral particles in cells that complement the missing protein(s), but do not produce infectious progeny virus. Such replicons can be useful for vaccine purposes.

Abstract: Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis.

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 virus, virus-like particle, viral capsid particle, phage or recombinant form thereof coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions. In one specific embodiment, a versatile new technology based on a cassette-type system (AlphaVaccine Technology) allows production of antigen coated viral particles. Other specific embodiments allow the production of antigen coated hepatitis B virus-like particles or antigen coated Measles virus-like particles.

Abstract: The present invention relates to genetically engineered recombinant respiratory syncytial viruses and viral vectors which contain deletions of various viral accessory gene(s) either singly or in combination. In accordance with the present invention, the recombinant respiratory syncytial viral vectors and viruses are engineered to contain complete deletions of the M2-2, NS1, NS2, or SH viral accessory genes or various combinations thereof. In addition, the present invention relates to the attenuation of respiratory syncytial virus by mutagenisis of the M2-1 gene.

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 recombinant vaccinia viruses derived from the modified vaccinia virus Ankara (MVA) and containing and capable of expressing foreign genes which are inserted at the site of a naturally occurring deletion in the MVA genome, and the use of such recombinant MVA viruses for the production of polypeptides, e.g. antigens or therapeutic agents, or viral vectors for gene therapy, and the use of such recombinant MVA viruses encoding antigens as vaccines.

Abstract: Vaccine formulations comprising viral capsomeres are disclosed along with methods for their production. Therapeutic and prophylactic methods of use for the vaccine formulations are also disclosed.

Abstract: This invention relates to attenuated pestiviruses characterised in that their enzymatic activity residing in glycoprotein ERNS is inactivated, methods of preparing, using and detecting these.

Abstract: The invention provides isolated polynucleotide molecules, including plasmids; viral vectors; and transfected host cells that comprise a DNA sequence encoding an infectious RNA sequence encoding a North American PRRS virus; and also North American PRRS viruses encoded thereby. The invention further provides isolated infectious RNA molecules encoding a North American PRRS virus. The invention also provides isolated polynucleotide molecules, infectious RNA molecules, viral vectors, and transfected host cells encoding genetically-modified North American PRRS viruses; and genetically-modified North American PRRS viruses encoded thereby. The invention also provides vaccines comprising such plasmids, RNA molecules, viral vectors, and North American PRRS viruses, and methods of using these vaccines in swine and in other animals. Also provided are isolated polynucleotide molecules, viral vectors, and transfected host cells that comprise a nucleotide sequence encoding a peptide of a North American PRRS virus.

Abstract: The present invention relates to a method for purifying recombinant HCV single or specific oligomeric envelope proteins selected from the group consisting of E1 and/or E2 and/or E1/E2, characterized in that upon lysing the transformed host cells to isolate the recombinantly expressed protein a disulphide bond cleavage or reduction step is carried out with a disulphide bond cleavage agent. The present invention also relates to a composition isolated by such a method. The present invention also relates to the diagnostic and therapeutic application of these compositions.

Abstract: Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural protein 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: 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 present invention relates to non-laboratory virus strains, for example of herpes viruses such as HSV, with improved oncolytic and/or gene delivery capabilities as compared to laboratory virus strains.

Abstract: A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes virus which: (i) lacks a functional vhs gene, or a functional equivalent thereof; (ii) lacks a functional ICP47 gene, or a functional equivalent thereof; and (iii) is incapable of expressing a substantial amount of functional ICP22, or a functional equivalent thereof, in mammalian dendritic cells.

Abstract: The invention is a series of synthetic virus-like particles comprising a heterologous conformational epitope useful in the characterization of human papillomavirus infection, and useful to vaccinate individual for protection against HPV 6 and HPV 11 infections, and assays employing the synthetic virus-like particles.

Abstract: The invention provides an equine infectious anemia (EIA) vaccine that provides immunity to mammals, especially equines, from infection with equine infectious anemia virus (EIAV) and which allows differentiation between vaccinated and non-vaccinated, but exposed, mammals or equines. Preferably said vaccine encompasses at least one mutation in an EIAV which produces a non-functional gene in the vaccine virus that is always expressed in disease-producing wild-type EIA viruses. Additionally, said EIA vaccine virus cannot cause clinical disease in mammals or spread or shed to other mammals including equines.

Abstract: The invention provides methods and compositions for inhibiting CMV infection and dissemination in an animal, as well as in vitro and in vivo assay systems for identifying such compositions.

Abstract: The present invention pertains to methods for preventing reovirus recognition in the treatment of cellular proliferative disorders, and particularly ras-mediated cellular proliferative disorders, in mammals. The method comprises suppressing or otherwise inhibiting the immune system of the mammal and, concurrently or subsequently, administering to the proliferating cells an effective amount of one or more reoviruses under conditions which result in substantial lysis of the proliferating cells. The methods may include the selective removal of immune constituents that may interfere with the systemic delivery of the virus; preventing reovirus recognition by the host immune system; and removal of the virus from an immune suppressed or immune incompetent host following treatment with reovirus. Alternatively, reovirus may be administered to a mammal with a diminished immune response system under conditions which result in substantial lysis of the proliferating cells.

Abstract: Mucin peptide epitopes are inserted into the coat protein of a plant virus (e.g., a comovirus such as CPMV) having a beta-barrel structure at an immunogenically effective site, such as in a loop connecting beta sheets or at/near the C-terminus. The resulting chimaeric virus particles are extremely immunogenic, giving better results than KLH conjugation and not requiring the addition of exogenous adjuvant. They are effective at mucosal surfaces, particularly when administered intranasally.

Abstract: The present invention provides genetically engineered type I/type II hybrid BVDV viruses. The hybrid viruses, as well as the hybrid viral genome, can be used in immunogenic compositions and vaccines for protecting cattle from BVDV infection.

Abstract: Genetic vaccines and methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one aspect, a method of enhancing the immunity of a host to a pathogen is provided. The method comprises administering to the host a recombinant virus comprising an antigen sequence that is heterologous to a native progenitor of the recombinant adenovirus and encodes a viral antigen from a pathogenic virus, expression of which is under the transcriptional control of a first promoter; and a cytokine sequence that is heterologous to the native progenitor of the recombinant adenovirus and encodes a cytokine, expression of which is under the transcriptional control of a second promoter. Expression of the antigen and cytokine sequences elicits an immune response directed against the viral antigen upon infection of the host by the recombinant virus.

Abstract: The invention relates to vaccines used in the eradication or control of pestivirus infections, particularly used in pigs or ruminants. The invention provides nucleic acid, pestivirus-like particles and a pestivirus vaccine, comprising the nucleic acid or particles, which is capable of eliciting a proper immune response without having the ability to spread throughout the vaccinated animal, thereby avoiding the negative consequences of viral spread. Preferably, the immunological response allows for serological discrimination between vaccinated animals and wild-type pestivirus infected animals.

Abstract: Recombinant respiratory syncytial virus (RSV) having the position of genes shifted within the genome or antigenome of the recombinant virus are constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome and are useful for eliciting an anti-RSV immune response. Shifting the position of genes in this manner provides for a selected increase or decrease in expression of the gene. In one embodiment, expression of RSV glycoproteins is upregulated by shifting one or more glycoprotein-encoding genes to a more promoter-proximal position. Genes of interest for manipulation to create gene position-shifted RSV include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment that may be part of a gene or extragenic. Additional mutations and nucleotide modifications are provided within gene position-shifted RSV to yield desired phenotypic and structural effects.

Abstract: The present invention relates i.a. to Bovine Respiratory Syncytial Viruses that are not capable of expressing a functional SH-protein and/or G-protein due to a mutation in the genes encoding the said proteins. Furthermore, the invention relates to vaccines based upon such Bovine Respiratory Syncytial Viruses and to methods for the preparation of such vaccines. Also the invention relates to diagnostic test kits for discriminating wild-type Bovine Respiratory Syncytial Viruses from Bovine Respiratory Syncytial Viruses according to the invention and to methods for the discrimination between those viruses.

Abstract: A method of producing an attenuated bovine respiratory syncytial virus (BRSV) having increased or decreased transcription and/or replication, as compared to a wild-type BRSV, including the steps of inserting a synthetic cDNA which codes for an infectious BRSV into a host cell, wherein the cDNA is operably-linked to a promoter; expressing the cDNA in the host cell to produce the infectious BRSV; and thereafter introducing at least one site-specific RNA point mutation on the P gene of the BRSV. An attenuated BRSV and vaccine produced by the method are also included.

Abstract: A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has at least two of the glycosylation sites proximal to the CD4 binding site or chemokine receptor site altered so that the alteration prevents glycosylation at that site or where glycosylation sites distal to these sites have been derivatized with a molecular adjuvant, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has both changes. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp 120.

Abstract: The inventive method of producing a eukaryotic viral vector comprises contacting a eukaryotic cell, which comprises a unique enzyme that nicks or cleaves a DNA molecule, with a recombinant phage vector, or contacting a eukaryotic cell, which does not comprise a unique enzyme that nicks or cleaves a DNA molecule, simultaneously or sequentially, in either order, with (i) a unique enzyme that nicks or cleaves a DNA molecule, and (ii) a recombinant phage vector. The recombinant phage vector comprises the DNA molecule comprising (a) a eukaryotic viral vector genome comprising a coding sequence, (b) a phage packaging site that is not contained within the eukaryotic viral vector genome, and (c) a promoter that is operably linked to the coding sequence. Alternatively, the DNA molecule is not present within the recombinant phage vector. The eukaryotic cell is contacted with the first DNA molecule and a recombinant phage vector.

Abstract: Recombinant hepatitis C virus (HCV) capsid proteins that self-assemble into large spherical virus-like particles structures and viral capsids that include conformational antigenic epitopes are provided. The large spherical virus-like particles structures and viral capsids, including capsid proteins that are expression products of a viral particle coding sequence protein, may be prepared as vaccines to induce a cellular or humoral immune response. The self assembling capsid proteins may also be used as elements of diagnostic immunoassay procedures for HCV infection.

Abstract: The present invention is directed to a cell line capable of supporting replication of a growth-defective Herpes Simplex Virus strain; specifically a replication-defective HSV-2 double mutant. Particularly disclosed is a cell line that expresses the ICP8 protein and the UL5 protein of Herpes Simplex Virus. This cell line is useful to propagate a replication-defective HSV-2 vaccine strain that contains mutations and/or deletions in the ICP8 and UL5 genes.