Abstract: A method of developing an immune response to HIV using a composition of inactivated HIV. Inactivation is through psoralen and ultraviolet radiation. The composition is rendered more effective by the removal of structural features of HIV that interfere with immune response. In particular, sialic acid is removed to enhance immune recognition of the composition and to impair Complement Factor H binding. CD55 and CD59 are also removed to prevent the binding of Complement Factor H. A method of developing an immune response to HIV using a composition of inactivated HIV. Inactivation is through psoralen and ultraviolet radiation. The composition is rendered more effective by the removal of structural features of HIV that interfere with immune response. In particular, sialic acid is removed to enhance immune recognition of the composition and to impair Complement Factor H binding. CD55 and CD59 are also removed to prevent the binding of Complement factor H.

Abstract: The invention refers to a recombinant oncolytic RNA Newcastle Disease Virus for the treatment of a proliferative disease, comprising at least one transgene coding for an avian cytokine, wherein the recombinant oncolytic RNA Newcastle Disease Virus is obtainable from a velogenic or mesogenic oncolytic RNA Newcastle Disease Virus. Virus-mediated expression of the cytokine in the natural host cells leads to a reduced pathogenicity of the virus for avian species. Furthermore the virus genome can encode binding proteins, prodrug-converting enzymes or/and proteases. The selective expression of these molecules in virus-infected tumor cells increases the anti-tumor effect of the virus.

Abstract: Compounds of formula I: wherein R1, R2, R2a, R3, R4 and R5 are defined herein, are useful as inhibitors of the HCV NS3 protease.

Abstract: The present invention relates to an isolated novel virus causing Severe Acute Respiratory Syndrome (SARS) in humans (“hSARS virus”). The hSARS virus is identified to be morphologically and phylogenetically similar to known member of Coronaviridae. The present invention provides the complete genomic sequence of the hSARS virus. Furthermore, the invention provides the nucleic acids and peptides encoded by and/or derived from the hSARS virus and their use in diagnostic methods and therapeutic methods, including vaccines. In addition, the invention provides chimeric or recombinant viruses encoded by said nucleotide sequences and antibodies immunospecific to the polypeptides encoded by the nucleotide sequences.

Abstract: A process for producing isolated and purified respiratory syncytial virus (RSV) fusion (F) and attachment (G) glycoproteins in eukaryotic cell cultures infected with RSV cold-passaged, temperature-sensitive mutant subgroup A2 strain cpts-248/404 results in at least a 5-fold increase in F and G protein yields when compared with the parent A2 strain. Immunogenic compositions comprising the F and/or G protein(s) produced by this process can be formulated for in vivo administration to a host to confer protection against disease caused by RSV.

Abstract: The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. In particular, the present invention provides for the use of agitation, high temperature, “stepped” depressurization, dialysis and dilution under pressure to increase the speed and extent of aggregate dissolution and protein refolding.

Abstract: A method for treating cancer cells is provided comprising directly or systemically administering a therapeutically effective dose of an attenuated measles virus. In one embodiment, the therapeutically effective dose is from about 103 pfus to about 1012 pfus and is delivered by direct injection into a group of cancer cells or via intravenous injection.

Abstract: The construction of recombinant respiratory syncytial virus (RSV) strains deleted of the region of G protein most likely to induce unwanted type 2 T cell responses in susceptible recipients is disclosed. Using reverse genetics, recombinant RSV strains were engineered with deletions of amino acids 151-221 and 178-219. Both RSV strains replicated in the respiratory tract of BALB/c mice and elicited serum neutralization and anti-F protein IgG titers that were equivalent to cp-RSV and contributed to a 3.9 log10 reduction in RSV A2 four days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either recombinant RSV strain. These findings are important for the development of immunogenic compositions against RSV.

Abstract: Recombinant enteroviruses for use as vaccines or vectors, which are modified in tropism or virulence, are disclosed. Also disclosed are DNA constructs comprising enterovirus-derived molecular determinants of tropism or virulence for use in targeting genes of interest to specific cells or tissues. The recombinant enteroviruses and DNA constructs comprise molecular determinants of tropism and virulence localized in specific domains of the 5?NTR of the enteroviral genome.

Abstract: The invention is directed to 5,6-dihydro-1H-pyridin-2-one compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

Abstract: A method of making an immunogenic composition using inactivated HIV. Inactivation of HIV is through psoralen and ultraviolet radiation. The composition is rendered more effective by the removal of structural features of HIV that interfere with immune response. In particular, sialic acid is removed to enhance immune recognition of the composition and to impair Complement Factor H binding. CD55 and CD59 are also removed to prevent the binding of Complement Factor H. A method of making an immunogenic composition using inactivated HIV. Inactivation of HIV is through psoralen and ultraviolet radiation. The composition is rendered more effective by the removal of structural features of HIV that interfere with immune response. In particular, sialic acid is removed to enhance immune recognition of the composition and to impair Complement Factor H binding. CD55 and CD59 are also removed to prevent the binding of Complement Factor H.

Abstract: The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9—; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is —C(?O)—, —O—C(?O)—, —NR8—C(?O)—, —O—C1-6alkanediyl-C(?O)—, —NR8—C1-6alkanediyl-C(?O)—, —S(?O)2—, —O—S(?O)2—, —NR8—S(?O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(?O), carboxyl, aminoC(?O), mono- or di(C1-4alkyl)aminoC(?O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; R5 and R6 are H or C1-6alkyl. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them.

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 relates to a cell-based method for producing influenza virus vaccines by enriching the population of surface-bound ?2,6-sialic acid receptors on a cell surface, such as on a Chinese Hamster Ovary (CHO) cell surface. The host cell therefore presents numerous binding sites to which an influenza virus can bind via its hemagglutinin spike protein and infect the host cell. In contrast to wild-type CHO cells, the surface of the mutated CHO cells of the present invention contains an enriched population of ?2,6-sialic acid receptors which makes the inventive CHO cells highly susceptible to viral infection, and therefore safe, effective, and highly efficient cells for rapidly producing influenza vaccines.

Abstract: The present invention is drawn to generating attenuated and less cytopathic forms of New World alphaviruses that can be used in immunogenic compositions as vaccines against both Old and New World alphaviruses. In this regard, the present invention discloses that the N-terminal, ˜35-aa-long peptide of VEEV, EEEV and, most likely, of WEEV capsid proteins plays the most critical role in the downregulation of cellular transcription and development of cytopathic effect. The identified, VEEV-specific peptide, CVEE30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of CVEE, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of CVEE by its SINV-specific counterpart in VEEV TC-83 genome does not affect virus replication in vitro, but makes it less cytopathic and more attenuated in vivo.

Abstract: The present invention relates to compositions and pharmaceutical compositions comprising poxviruses and more particularly extracellular enveloped viruses. The present invention also relates to a process for producing poxviruses and poxviruses obtained thereof. Moreover, the present invention also relates to the use of said poxvirus and said composition for the preparation of a medicament.

Abstract: The invention is related to compounds of Formula I or a pharmaceutically acceptable salt, solvate, ester, and/or phosphonate thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

Abstract: The invention relates inter alia to a method for inducing a long-term protection in an animal against foreign antigens and tumor antigens comprising the step of administering to the animal at least one factor selected from type I interferons and Flt-3, and to a method for inducing a long-term increase of the number of dendritic cells in an animal comprising the step of administering to the animal a factor selected from type I interferon and Flt-3 and to a method of inducing or enhancing the maturation and/or for the activation of the immune system of an animal comprising the step of administering to the animal a factor selected from type I interferon and Flt-3.

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.

Abstract: The present invention discloses a novel apathogenic viral strain useful in the treatment of viral hepatitis infections. The preferred viral strain of Infectious Bursal Disease Virus (IBDV) is specifically characterized in terms of structure and biological activities. The invention also provides recombinant IBDV viral vectors for the inclusion of exogenous nucleic acid sequences enhancing the viral replication inhibitory effect of the virus of the invention. Preferably, the viral vector comprises a nucleic acid sequence encoding a cytokine. A method of treating viral hepatitis in a host comprising administering an anti-hepatitis effective amount of the IBDV strain of the present invention also provided.

Abstract: A vaccine against nodavirus infection in fish can be produced by inactivating the virus using an aziridine compound. This vaccine can be used to prevent Viral Nervous Necrosis (VNN) in a variety of fish species.

Abstract: The present invention provides a cDNA of a severe acute respiratory syndrome (SARS) coronavirus, recombinant SARS coronavirus vectors, and SARS coronavirus replicon particles. Also provided are methods of making the compositions of this invention and methods of using the compositions as immunogens and/or vaccines and/or to express heterologous nucleic acids.

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: In certain aspects, the present invention provides methods for increasing the replication capacity of influenza viruses in hens' eggs and/or cell culture, recombinant and/or reassortant influenza viruses with increased replication capacity, and immunogenic and vaccine compositions comprising such recombinant and/or reassortant influenza viruses. In other aspects, the invention further provides nucleic acids encoding influenza genes associated with increased replication capacity, expression vectors comprising the nucleic acids of the invention, methods for making influenza viruses with increased replication capacity, and kits useful for practice of the methods.

Abstract: The present invention provides an isolated mammalian negative strand RNA virus, metapneumovirus (MPV), within the sub-family Pneumoviridae, of the family Paramyxoviridae. The invention also provides isolated mammalian negative strand RNA viruses identifiable as phylogenetically corresponding or relating to the genus Metapneumovirus and components thereof. In particular the invention provides a mammalian MPV, subgroups and variants thereof. The invention relates to genomic nucleotide sequences of different isolates of mammalian metapneumoviruses, in particular human metapneumoviruses. The invention relates to the use of the sequence information of different isolates of mammalian metapneumoviruses for diagnostic and therapeutic methods. The present invention relates to nucleotide sequences encoding the genome of a metapneumovirus or a portion thereof, including both mammalian and avian metapneumovirus. The invention further encompasses chimeric or recombinant viruses encoded by said nucleotide sequences.

Abstract: A method to prepare viruses with a mutant membrane protein gene, and viruses obtained by the method, are provided.

Abstract: Compositions and methods are provided that relate to an attenuated reovirus exhibiting oncolytic activity toward cancer cells while displaying reduced lytic activity toward non-malignant cells. Exemplified is an attenuated human reovirus derived from persistently infected fibrosarcoma cells that lacks wild-type reovirus S1 and S4 genes and consequently lacks a detectable reoviral outer capsid ?1 protein and expresses a mutated reoviral outer capsid ?3 protein.

Abstract: This application provides a method to form non-infectious Biological Carrier that may be used to deliver signals to cells either in vitro or in vivo. The Biological Carriers are inactivated virus particles that have been specifically modified to give biological properties different from the virus particles deriving from an unmodified host cell that (i) expresses at least one co-stimulatory molecule and (iia) at least one antigen that can initiate an immune response, and/or (iib) express surface molecules that suppress viral replication.

Abstract: Attenuated pestiviruses, in particular attenuated BVDV, wherein at least one mutation is in the coding sequence for glycoprotein Erns and at least another mutation in the coding sequence for Npro which preferably leads to combined inactivation of the RNase activity residing in glycoprotein Erns in addition to the inactivation of the (hypothesized) immunomodulating activity residing in Npro. Methods for attenuating pestiviruses such as BVDV, nucleic acids encoding the pestiviruses, in particular BVDV, compositions and vaccines comprising the attenuated pestiviruses, in particular BVDV, of the invention.

Abstract: The present invention relates to methods for treating or preventing diseases or disorders in a pregnant cow and calf nursing a pregnant cow caused by infection by Bovine Viral Diarrhea Virus (BVDV) Types 1 and 2, Bovine Herpes Virus Type-1 (BHV-1), Bovine Respiratory Syncytial Virus (BRSV), Parainfluenza Virus (PIV3), Campylobacter fetus, Leptospira canicola, Leptospira grippotyphosa, Leptospira borgpetersenii hardjo-prajitno, Leptospira icterohaemorrhagia, Leptospira hardjo-bovis and Leptospira pomona by administering to the animal an effective amount of a safe modified live viral combination vaccine further combined with a multivalent bacterin vaccine.

Abstract: A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.

Abstract: An antigenic and immunogenic composition of predetermined inactivated strains of human immunodeficiency virus (HIV) is disclosed. Inactivation is through psoralen and ultraviolet radiation; the composition is rendered more effective by the removal of structural features of HIV that interfere with immune response. In particular, sialic acid is removed to enhance immune recognition of the composition and to impair Complement Factor H binding. CD55 and CD59 are also removed to prevent the binding of Complement Factor H. Determination of strains for inactivation may be though immunotherapeutic genotyping or probabilistic assessment of risk of exposure.

Abstract: The invention relates to the field of coronaviruses and diagnosis, therapeutic use, and vaccines derived therefrom. The invention provides replicative coronaviruses and virus-like particles (VLPs) from which large parts of their genome are (at least functionally) deleted without abolishing their replicative capacities. The deletion preferably results in at least a functional deletion in that the corresponding gene is not or is only partly expressed wherein the resulting gene product is dysfunctional or at least functionally distinct from a corresponding wild-type gene product.

Abstract: Influenza virus-like particles (VLPs) comprising the structural proteins HA, NA, M1 and M2 are described. VLPs are also generated containing M1 alone, as are VLPs with M1 and any one or two of HA, NA and M2. VLPs with HA from one influenza subtype and NA from a different influenza subtype are also described, as are VLPs in which a portion or all of HA or NA is replaced by a heterologous moiety not produced by influenza virus, so as to comprise chimeric VLPs.

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

Abstract: The present invention provides a genetically modified PRRS virus, methods to make it and related polypeptides, polynucleotides and various components. Vaccines comprising the genetically modified virus and polynucleotides are also provided.

Abstract: A mutant virus is provided which contains a mutation at a phosphorylation site in one or more of the proteins of the virus, which mutation causes the virus to be attenuated, and therefore, an improved vaccine composition can be produced therewith. The invention also relates to vaccine compositions which contain the mutant virus, as well as to methods of inducing an immune response, and of protecting mammals from infection by rabies virus. Also included in the invention are methods of producing the mutant virus and mutant viral proteins, including producing the mutant virus in a host cell which produces or even overproduces a wild-type counterpart of the mutant viral protein, which complements the other viral proteins such that production of the mutant viral particle is optimized.

Abstract: Reagents and methods for making and using HIV recombinant vaccines are disclosed.

Abstract: The present invention discloses Moloney murine leukemia virus (MoMLV)-based viral packaging cell line for the production of anti-viral vaccines. The invention also includes methods of making, administering and formulating pseudovirions and replicon deficient viral particles of the invention and methods of inducing immunity.

Abstract: The present invention provides recombinant respiratory syncytial viruses that have an attenuated phenotype and that comprise one or more mutations in the viral P, M2-1 and/or M2-2 proteins, as well as live attenuated vaccines comprising such viruses and nucleic acids encoding such viruses. Recombinant RSV P, M2-1 and M2-2 proteins are described. Methods of producing attenuated recombinant RSV, and methods of quantitating neutralizing antibodies that utilize recombinant viruses of family Paramyxoviridae, are also provided.

Abstract: Means and methods for producing mammalian viruses, the method comprising infecting a culture of immortalized human cells with a virus, incubating the culture infected with virus to propagate the virus under conditions that permit growth of the virus, and to form a virus-containing medium, and removing the virus-containing medium. The viruses can be harvested and be used for the production of vaccines. Advantages include that human cells of the present invention can be cultured under defined serum-free conditions and the cells show improved capability for propagating virus. Methods are provided for producing, in cultured human cells, influenza virus and vaccines derived thereof. This method eliminates the necessity of using whole chicken embryos for the production of Influenza vaccines. The method also provides for the continuous or batch-wise removal of culture media. As such, the present invention allows the large-scale continuous production of viruses to a high titer.

Abstract: The present invention relates to methods for killing neoplastic cells, such as ras-activated cancerous cells, in vitro. In particular embodiments, an attenuated reovirus (e.g., a reovirus lacking a wild-type S1 gene) may be administered to a mixed cellular composition comprising cancerous cells and stem cells such as adult stem cells and/or hematopoietic stem cells; in these embodiments, the attenuated reovirus may result in killing of the cancerous cells with little or no damage to the healthy stem cells.

Abstract: The invention relates to influenza virus vaccines, and in particular to a reassortant influenza virus which has at least its hemagglutinin gene derived from a non-pathogenic or low pathogenic influenza virus, and its other genes derived from a donor strain. In one embodiment the influenza virus is a 7:1 reassortant, in which only the hemagglutinin gene is derived from a non-pathogenic influenza virus. The virus is useful for production of vaccines against influenza, including influenza caused by highly pathogenic influenza virus strains.

Abstract: Modified or attenuated viruses and methods for preparing the modified viruses and modulating attenuation are provided. Vaccines that contain the viruses are provided. The viruses can be used in methods of treatment of diseases, such as proliferative and inflammatory disorders, including as anti-tumor agents. The viruses also can be used in diagnostic methods.

Abstract: The invention relates to the production of coronaviruses.

Abstract: The invention relates to a dengue virus tetravalent vaccine containing a common 30 nucleotide deletion (?30) in the 3?-untranslated region of the genome of dengue virus serotypes 1, 2, 3, and 4, or antigenic chimeric dengue viruses of serotypes 1, 2, 3, and 4.

Abstract: Described is a polynucleotide molecule being a fragment of a polynucleotide sequence of an infectious human endogenous retrovirus, said polynucleotide molecule comprising a sequence selected from the group consisting of (a) a sequence with at least 98%, preferably 99%, still preferred 99.5%, identity to a sequence according to SEQ ID No 1, (b) a sequence which hybridises under stringent conditions with a nucleotide sequence according to said SEQ ID No 1, (c) a sequence which differs from said sequences (a) or (b) due to degeneration of the genetic code and (d) a sequence comprising sequences inserted into vectors pCR4-Topo and deposited as “MERV-env”, “MERV-gag”, “MERV-prt” and “MERV-pol” at the DSMZ on 26 Sep. 2001 or fragments thereof.

Abstract: The present invention is directed to novel avian pneumovirus strain Colorado (APV/CO) genes and intergenic sequences. Also disclosed are methods of making recombinant avian pneumovirus and live-attenuated APV/CO. Further disclosed are methods of diagnosing avian pneumovirus.

Abstract: The invention provides chimeric flavivirus vaccines against West Nile virus and methods of using these vaccines to prevent or treat West Nile virus infection.

Abstract: Provided herein are phosphadiazine polymerase inhibitor, for example, of Formula III, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.