Abstract: The present invention provides methods for the purification of cell-associated viruses from adherent cells (e.g., MDCK or Vero cells). In particular, the present invention provides purification methods for the production of immunogenic compositions comprising a live attenuated cell-associated virus (e.g., an attenuated respiratory syncytial virus (RSV) or cold-adapted, and/or temperature sensitive influenza virus) that result in levels of host cell DNA (HCD), host cell protein (HCP) and non-specific endonuclease (e.g., Benzonase), which are below the specifications required by regulatory agencies. The immunogenic compositions can be used to actively immunize subjects or to generate antibodies for a variety of uses, including passive immunization and diagnostic immunoassays.

Abstract: A method for purification of viral compositions is provided. In particular, a method for reduction of unwanted residual DNA in a viral composition while retaining the immunogenicity of the virus itself is provided. The resulting immunogenic viral composition is substantially free of residual DNA, and is useful for the manufacture of medical products, such as vaccines designed for human or animal.

Abstract: There is provided an HSV complex which comprises an avirulent HSV and a targeting agent which allows the HSV particle to infect and lyse a specific targeted cell. The inventors have found a way in which avirulent HSV can be targeted to disease cells, e.g. cancer cells, by incorporating an antibody binding domain into one or more viral glycoproteins.

Abstract: Provided is a vaccine against respiratory syncytial virus (RSV), comprising a recombinant human adenovirus of serotype that comprises nucleic acid encoding a RSV F protein or immunologically active part thereof.

Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.

Abstract: We have generated novel molecularly marked FMDV A24LL3DYR and A24LL3BPVKV3DYR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3Dpol and 3B proteins. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. The mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR. Cattle immunized with chemically inactivated vaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine. These vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.

Abstract: Described herein are iDNA vectors and vaccines and methods for using the same. The iDNA generates live attenuated vaccines in eukaryotic cells in vitro or in vivo for pathogenic RNA viruses, particularly yellow fever virus and Venezuelan equine encephalitis virus. When iDNA is injected into the vaccine recipient, RNA of live attenuated virus is generated by in vivo transcription in the recipient's tissues. This initiates production of progeny attenuated viruses in the tissues of the vaccine recipient, as well as elicitation of an effective immune response protecting against wild-type, non-attenuated virus.

Abstract: The present invention is directed to an improved method of purifying virus, particularly reovirus. Infectious virus can be extracted from a cell culture with a detergent to produce high titers of virus, and the virus can then be purified by simple steps such as filtration and column chromatography. Viruses and compositions comprising the viruses prepared according to the present invention are also provided.

Abstract: A method of preparing a capturing agent for a selected biopolymer or bioparticle, includes the steps of: a) selecting a desired biopolymer or bioparticle, and b) providing a support matrix modified to have, at predetermined conditions, such a net negative surface charge and net surface hydrophobicity in relation to the net negative surface charge and the net surface hydrophobicity of the selected biopolymer or bioparticle that the modified support matrix is capable of selective interaction and capture of the biopolymer or bioparticle through a resulting net hydrophobic interaction being the actual hydrophobic interaction minus the actual electrostatic repulsion. The use of such a capturing agent as a therapeutically active substance, as well as in chromatography and diagnosis are also disclosed.

Abstract: Certain embodiments are directed to viral production processes for the large scale production of vaccinia virus.

Abstract: The invention is directed to an improved method to manufacture virus for use in vaccine by culturing infected cells that have been modified to overexpress miR-144. The invention is also directed to manipulating the activity or level of miR-144 in subjects in order to modulate the antiviral and immune response systems.

Abstract: The present invention provides novel MDCK-derived adherent non-tumorigenic cell lines that can be grown in the presence or absence of serum. The cell lines of the present invention are useful for the production of vaccine material (e.g., viruses). More specifically, the cell lines of the present invention are useful for the production of influenza viruses in general and ca/ts influenza viruses in particular. The invention further provides methods and media formulations for the adaptation and cultivation of MDCK cells such that they remain non-tumorigenic. Additionally, the present invention provides methods for the production of vaccine material (e.g., influenza virus) in the novel cell lines of the invention.

Abstract: The present invention relates to molecular biology, molecular genetics, and bioprocessing. The embodiments provide for compositions and methods for producing a biological product, such as an immunogenic agent, in an embryonated egg by introducing into the egg a RNA effector molecule capable of modulating expression of a target gene, wherein the modulation enhances production of the biological product in the egg. These methods provide for RNAi-based approaches to optimize the production of biologics from embryonated eggs, such as the production of viral vaccines including seasonal and pandemic flu vaccines. The invention also relates to molecules, reagents, cells, and kits useful for carrying out the methods, and biological products produced by the methods.

Abstract: The present invention relates to the development and manufacturing of viral vaccines. In particular, the invention relates to the field of industrial production of viral vectors and vaccines, more in particular to the use of avian embryonic stem cells, preferably the EBx® cell line derived from duck embryonic stem cells, for the production of viral vectors and viruses. The invention is particularly useful for the industrial production of viral vaccines to prevent viral infection of humans and animals.

Abstract: The present invention is directed to a modified poxvirus vector that allows for the generation of recombinant poxviruses by a single recombination event. A modified poxvirus vector comprising at least one reporter gene located between two flanking sequences for homologous recombination is disclosed. Furthermore, a host cell comprising said vector and a method for the generation of recombinant poxviruses using said vector are provided.

Abstract: The present invention provides methods and compositions related to the generation of host cells permissive for virus growth, particularly Porcine Reproductive and Respiratory Syndrome (PRRS) virus.

Abstract: Vectors and methods for the production of influenza viruses suitable as recombinant influenza vaccines in cell culture are provided. Bi-directional expression vectors for use in a multi-plasmid influenza virus expression system are provided. Additionally, the invention provides methods of producing influenza viruses with enhanced ability to replicate in embryonated chicken eggs and/or cells (e.g., Vero and/or MDCK) and further provides influenza viruses with enhanced replication characteristics. A method of producing a cold adapted (ca) influenza virus that replicates efficiently at, e.g., 25° C. (and immunogenic compositions comprising the same) is also provided.

Abstract: Vectors and methods for the production of influenza viruses suitable as recombinant influenza vaccines in cell culture are provided. Bi-directional expression vectors for use in a multi-plasmid influenza virus expression system are provided.

Abstract: Methods and compositions for the optimization and production of refrigerator-temperature stable virus, e.g., influenza, compositions are provided. Formulations and immunogenic compositions comprising refrigerator-temperature stable virus compositions are provided.

Abstract: The invention provides compositions and methods useful to prepare segmented, negative strand RNA viruses, e.g., orthomyxoviruses such as influenza A viruses, entirely from cloned cDNAs and in the absence of helper virus.

Abstract: The present invention aims to provide a method which enables efficient removal of impurities such as the host proteins from an influenza virus culture liquid by a simple operation, allowing separation and purification of an influenza virus antigen. The method of the present invention for producing a purified influenza virus antigen comprises the step of treating a sample containing an influenza virus with a surfactant, the step of bringing the sample after the treatment into contact with hydroxyapatite in the presence of the surfactant, and the step of recovering a hydroxyapatite-non-adsorbed fraction.

Abstract: The present invention relates to a method for inactivating virus in a sample by treating a virus containing sample with an effective concentration of formalin and by treating the sample with an effective dose of UV light in a flow-through apparatus.

Abstract: The invention provides a method of increasing product yield per culture in a population of product-secreting cells bound to a scaffold, for example, a microcarrier, at least partially immersed in a culture medium in a bioreactor. The method comprising: semi-harvesting product by removing a volume of the culture medium with a first-secreted product concentration while leaving the scaffold with the bound cells in the bioreactor; re-feeding the cells by adding a fresh culture medium to increase the culture medium in the bioreactor to approximately the original volume; agitating the culture medium to allow the cells to grow and release a second-secreted product concentration; harvesting product by removing the culture medium with the second-secreted product concentration while leaving the scaffold with the bound cells behind. Also disclosed is a method of increasing virus yield per culture in a population of virus-infected cells bound to a microcarrier suspended in a culture medium.

Abstract: The invention provides an isolated H3 equine influenza A virus, as well as methods of preparing and using the virus, and genes or proteins thereof.

Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.

Abstract: The present invention is directed to an improved method of purifying virus, particularly reovirus. Infectious virus can be extracted from a cell culture with a detergent to produce high titers of virus, and the virus can then be purified by simple steps such as filtration and column chromatography. Viruses and compositions comprising the viruses prepared according to the present invention are also provided.

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: Polypeptides, polynucleotides, reassortant viruses, immunogenic compositions and vaccines comprising influenza hemagglutinin and neuraminidase variants and method using thereof are provided.

Abstract: The present invention relates to a method for the cultivation of primary cells. The primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The method for the cultivation of primary cells may be one step in a method for the amplification of viruses, such as poxviruses. According to this latter method the primary cells are cultivated in a serum free medium comprising a factor selected from the group consisting of growth factors and attachment factors. The cells are then infected with the virus and the infected cells are cultivated in serum free medium until progeny virus is produced.

Abstract: The present invention relates to compositions and methods for producing an immune response or reaction, as well as to vaccines, kits, processes, cells and uses thereof. This invention more particularly relates to compositions and methods of using a synthetic viral particle to produce, modify or regulate an immune response in a subject. In a more preferred embodiment, the invention is based, generally, on compositions using synthetic viral particles as an adjuvant and/or vehicle to raise an immune response against selected antigen(s) or epitopes, in particular a cellular and/or a humoral immune response.

Abstract: The present invention encompasses methods of producing influenza B viruses in cell culture. The influenza B viruses may have desirable characteristics, such as enhanced replication in eggs and may be used, for example, in vaccines and in methods of treatment to protect against influenza B virus infection.

Abstract: Described is a composition comprising a plurality of recombinant adenovirus particles, being a recombinant human adenovirus of serotype 5, 26, 34, 35, 48, 49 or 50, or a recombinant simian adenovirus, characterized in that the genomes of essentially all adenovirus particles in the composition comprise as the 5? terminal nucleotides the nucleotide sequence: CTATCTAT (nucleotides 1-8 of SEQ ID NO:7). Also described are methods to produce such compositions.

Abstract: Highly efficient and rapid filtration-based concentration devices, systems and methods are disclosed with sample fluidic lines and a filter packaged in a disposable tip which concentrate biological particles that are suspended in liquid from a dilute feed suspension. A sample concentrate or retentate suspension is retained while eliminating the separated fluid in a separate flow stream. The concentrate is then dispensed from the disposable tip in a set volume of elution fluid. Suspended biological particles include such materials as proteins/toxins, viruses, DNA, and/or bacteria in the size range of approximately 0.001 micron to 20 microns diameter. Concentration of these particles is advantageous for detection of target particles in a dilute suspension, because concentrating them into a small volume makes them easier to detect. All conduits by which the disposable tip attaches to the instrument are combined into a single connection point on the upper end of the tip.

Abstract: The present invention relates to a method for producing and purifying a wild type, an attenuated and/or a recombinant Orthopoxvirus.

Abstract: The present invention provides system and methods for detecting an analyte indicative of an influenza viral infection in a sample of bodily fluid. The present invention also provides for systems and method for detection a plurality of analytes, at least two of which are indicative of an influenza viral infection in a sample of bodily fluid.

Abstract: There is provided a safe, natural, environmentally sound means of controlling bacterial contamination, corrosion, and souring of oil and gas wells and reservoirs that result from bacteria-contaminated water in a well. In one aspect it is a process for remediation of souring of petroleum reservoirs and coalbeds by adding to the water used in flooding and “fracing” operations an effective amount of virulent (non-lysogenic) bacteriophages (phages) specific for problematic target bacteria. The invention also provides a means for combating loss of effectiveness of bacterial control by staging bacteriophage production and application to control dominant and sub-dominant target bacteria in a community of target bacteria.

Abstract: Bacteriophages in general and lambda phage in particular are powerful, flexible reagents who have yet to be exploited to their full potential. As discussed herein, the lambda phage head and/or genome comprises an easy to use and highly efficient delivery vehicle for delivering the expression products of a gene of interest systemically or to a particular tissue.

Abstract: The present invention relates to recombinant cells as well as to methods for the generation of non-segmented negative-sense single-stranded RNA viruses (NNV or mononegavirales) from cloned deoxyribonucleic acid (cDNA), especially from measles virus and in particular from attenuated strains such as those approved for vaccination, in particular from the attenuated Schwarz measles virus and various recombinant Schwarz measles-based viruses expressing heterologous sequences. Such rescued viruses can be used, after amplification, as vaccines for immunization against measles and/or against the heterologous peptides or proteins expressed.

Abstract: Methods and compositions for the optimization and production of refrigerator-temperature stable virus, e.g., influenza, compositions are provided. Formulations and immunogenic compositions comprising refrigerator-temperature stable virus compositions are provided.

Abstract: New influenza donor strains for the production of reassortant influenza A viruses are provided.

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

Abstract: The present invention provides a nucleic acid molecule comprising a nucleotide sequence encoding an infectious RNA molecule encoding a live viral strain of a dengue 3 virus (DV3), wherein said nucleotide sequence is the nucleotide sequence of SEQ ID NO:1 or a nucleotide sequence having at least 99% identity with the nucleotide sequence of SEQ ID NO.1.

Abstract: Methods for production of virus particles with simplified glycosylation on structural or surface proteins are provided. When used as targets for vaccine production, the conserved nature of such sites generates vaccines that are less sensitive to viral mutations. Use of glycosylation inhibitors for production of viruses with simplified glycosylation profiles are disclosed. An exemplary disclosure of influenza viruses and methods for production of mono-glycosylated influenza virus particles is provided. Methods for production of mono-glycosylated forms of influenza A virus, NIBRG-14 (H5N1) are provided.

Abstract: Polyethyleneimine and polyalkylene biguanide ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: Polypeptides, polynucleotides, reassortant viruses, immunogenic compositions and vaccines comprising influenza hemagglutinin and neuraminidase variants and method using thereof are provided.

Abstract: The present invention relates to a method for producing and purifying a wild type, an attenuated and/or a recombinant Orthopoxvirus. The present invention relates to a purified wild type, attenuated and/or recombinant Orthopoxvirus obtained by the method of the invention and to a pharmaceutical composition, preferably a vaccine, comprising said purified Orthopoxvirus for the treatment and/or the prevention a cancer, an infectious disease and/or an autoimmune disorder, and uses thereof. The present invention also relates to the use of an immortalized avian cell line obtained from an avian cell belonging to the Anatidae family, in particular Cairina moschata immortalized avian cell lines comprising a nucleic acid sequence coding a telomerase reverse transcriptase (TERT) and optionally an E1A nucleic acid sequence, for the production of a wild type, attenuated and/or recombinant Orthopoxvirus according to the process of the invention.

Abstract: The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.

Abstract: The present invention relates to the field of vaccines and medicaments for the prophylaxis and treatment of infectious diseases in ruminants. In particular, it relates to inactivated Schmallenberg virus (SBV) useful as vaccine or medicament for preventing or treating viremia, the transmission and clinical symptoms, in particular malformations in newborn ruminants such as cattle, sheep and goats, induced by SBV.