Abstract: This invention relates to infectious chimeric papillomaviruses, and especially those where the early genes are from human papillomavirus (HPV) 18, and the late genes are from another HPV. Also presented are methods of culturing the virus in raft cell cultures, and to assays utilizing these chimeric viruses.

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: A vaccine for protecting a horse against diseases associated with EHV-1 and/or EHV-4 is provided. The vaccine commonly includes inactivated EHV-1 (e.g., chemically inactivated EHV-1 KyA virus) and an adjuvant. The adjuvant can include a cross-linked olefinically unsaturated carboxylic acid polymer which may have bioadhesive properties. The vaccine may also include antigens against other equine pathogens such as inactivated EHV-4 and inactivated A1 and/or A2 strains of equine influenza virus. Methods for protecting horses against diseases associated with EHV-1 and/or EHV-4 and methods of producing the equine herpesvirus vaccine are also provided.

Abstract: The present invention relates to pharmaceutical compositions, kits, and methods of use thereof, comprising, a mutant human herpes simplex virus, which is cytopathic to susceptible target cells, such as neoplastic cells. Preferably, the virus does not produce a functionally active wild-type gC polypeptide coded for the UL44 gene.

Abstract: An attenuated herpes virus which lacks a functional vhs gene or a functional equivalent thereof, but which has a functional UL43 gene or functional equivalent thereof, stimulates an immune response when dendritic cells are infected with the virus.

Abstract: Recombinant respiratory syncytial virus (RSV) are provided in which expression of the second translational open reading frame encoded by the M2 gene (M2ORF2) is reduced or ablated to yield novel RSV vaccine candidates. Expression of M2 ORF2 is reduced or ablated by modifying a recombinant RSV genome or antigenome to incorporate a frame shift mutation, or one or more stop codons in M2 ORF2. Alternatively, M2 ORF2 is deleted in whole or in part to render the M2-2 protein partially or entirely non-functional or to disrupt its expression altogether. M2 ORF2 deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in mRNA transcription, genomic or antigenomic RNA replication, viral growth characteristics, viral antigen expression, viral plaque size, and/or a change in cytopathogenicity.

Abstract: Recombinant respiratory syncytial virus (RSV) are provided which express one or more immune modulatory molecules. The recombinant virus is modified by addition or substitution of a polynucleotide sequence encoding the immune modulatory molecule, which is preferably a cytokine. Introduction of the cytokine increase, decrease, or otherwise enhances aspects of viral biology and/or host immune responses to RSV to facilitate vaccine use of the virus. Cytokines for use within the invention include but are not limited to interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL6), or interleukin 18 (IL-18), tumor necrosis factor (TNF) alpha, interferon gamma (IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF).

Abstract: A live hepatitis A virus adapted to growth in MRC-5 cells, which HAV is preferably characterized by suitable attenuation for effective vaccine administration to humans and animals without inactivation, methods for adapting HAV to growth in MRC-5, vaccine compositions and method of vaccinating humans against HAV infection.

Abstract: The present invention relates to herpes simplex virus (HSV) amplicon vectors, and in particular, HSV-1 amplicon vectors, which have been genetically modified and used alone or with consequent genetically modified HSV virus, to target a selected cell type, such as neoplastic cells. The present invention also relates to methods of using such vectors to target a cell, in order to treat a pathologic condition, such as cancer.

Abstract: An agent for combating an intracellular microbial infection comprises a phage component and, associated therewith, a targeting moiety which directs the agent to a target cell and initiates delivery of the phage into the target cell. Once inside the target cell, the phage causes lysis of a microorganism residing within the target cell. A mycobacteriophage is combined with a targeting moiety of transferrin. Compositions comprising the agent, methods of preparing said agent, and use of said agent for combating intracellular infections are also provided.

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: Methods for treating cell proliferative disorders by administering virus to proliferating cells having an activated Ras-pathway are disclosed. The virus is administered so that it ultimately directly contacts proliferating cells having an activated Ras-pathway. Proliferative disorders include but are not limited to neoplasms. The virus is selected from modified adenovirus, modified HSV, modified vaccinia virus and modified parapoxvirus orf virus. Also disclosed are methods for treating cell proliferative disorders by further administering a immunosuppressive agent.

Abstract: The invention relates to a method for enhancing the specific immune response against an immunogenic compound which comprises administering the immunogenic compound together with a poxvirus recombinant and a vaccinal antigen, which is not a poxvirus. The immunological material may be any biological material useful as a vaccine e.g., a polypeptide characteristic of a pathogenic microorganism or associated with a tumoral disorder, a DNA plasmid encoding a peptide or a polypeptide characteristic of a pathogenic microorganism or a tumor-associated antigen, or an hapten coupled to a carrier molecule. The poxvirus may be a live, attenuated or inactivated virus or a recombinant virus. Recombinant virus may encode a heterologous polypeptide such as chemokines, cytokines or co-immunostimulatory molecules or an homologous polypeptide, which is immunologically cross reactive with the immunogenic polypeptide or peptide.

Abstract: An attenuated herpes virus capable of efficiently infecting a dendritic cell without preventing antigen processing occurring within the infected cell. The attenuated herpes virus and dentrictic cells infected with the virus are useful in immunotherapeutic methods of treating disease.

Abstract: This invention relates to the fields of genetic engineering, virus replication and gene transfer. More specifically, this invention relates to polynucleotide construct, recombinant virus, transposon, and their vectors, wherein an ori derived from a DNA virus capable of replicating in vertebrate cells is inserted into the retrovirus, allowing the retrovirus following the reverse transcription to efficiently replicate as extrachromosomal or episomal DNA without the necessity of integration into the host cell chromosome. Additionally, this invention relates to polynucleotide construct, recombinant virus, transposon, and their vectors replicating episomally without aid of an ori and related elements. Also, this invention encompasses preventive, therapeutic, and diagnostic applications employing said constructs, viruses and vectors.

Abstract: The present invention relates to (a) methods for improving a genetic stability of an insert nucleotide sequence in a recombinant single-stranded RNA virus vector, which comprises performing a mutagenesis of the foreign insert nucleotide sequence to provide even distribution of G/C content throughout the overall foreign insert nucleotide sequence and/or to increase G/C content of the foreign insert without substantially causing amino acids substitutions (b) a recombinant single-stranded RNA virus comprising an insert nucleotide sequence with improved genetic stability and (c) a recombinant poliovirus comprising an insert nucleotide sequence with improved genetic stability.

Abstract: A live, attenuated chimeric virus vaccine against tick-borne encephalitis virus comprising the preM and E structural genes of the tick-borne encephalitis Langat virus and the non-structural genes of the mosquito-borne dengue virus. The live chimeric vaccine was administered intraperitoneally and exhibited complete attenuation in mice while at the same time providing protection against subsequent challenge with the virulent parental Langat virus.

Abstract: Disclosed is a measles virus mutant gene coding for a measles virus mutant H protein antigen, wherein said gene coding for a measles virus mutant H protein antigen is at least one member selected from the group consisting of the following genes (a) to (c): (a) a gene coding for an amino acid sequence of SEQ ID NO: 10; (b) a gene coding for an amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 11; and (c) a gene coding for an amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 12. By the use of the measles virus mutant gene of the present invention, it has become possible to provide efficiently and economically a gene vaccine which is adapted for an epidemic strain of measles virus, and a diagnostic reagent capable of accurately detecting infections with an epidemic strain of measles virus.

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: Novel HCV peptide antigens are described representing partial sequences of the C-100-3 and env/core with C-regions. These peptide antigens are suitable for the determination of HCV antibodies as immunogens for the production of antibodies against HCV and as vaccines for the production of vaccines against HCV.

Abstract: Processes and systems for the high throughput directed evolution of peptides and proteins, particularly those that act in complex biological settings, are provided. The proteins and peptides include, but are not limited to, intracellular proteins, messenger/signaling/hormone proteins and viral proteins. Also provided is a rational method for generating protein variants and also a method for titering viruses.

Abstract: The present invention is directed toward genetically-engineered, membrane-enveloped Alphaviruses, Flaviviruses, and Bunyaviruses containing modified viral transmembrane envelope glycoproteins (e.g., E2, E1, E, and G) and bearing altered host-range phenotypes that enables the viruses to replicate efficiently in insect cells, but not mammalian cells. The strategy for production of these mutations is based on the fact that unlike mammalian cell membranes, the membranes of insect cells contain no cholesterol and are thus thinner than mammalian membranes. Many membrane-coated viruses have membrane glycoproteins on their surface which are responsible for identifying and infecting target cells. These membrane glycoproteins have hydrophobic membrane-spanning domains which anchor the proteins in the membrane bilayer. The membrane-spanning domains of these transmembrane proteins must be long enough to reach from one side of the bilayer to the other in order to hold the proteins in the membrane.

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 present invention provides experimentally-generated cold-adapted equine influenza viruses, and reassortant influenza A viruses comprising at least one genome segment of such an equine influenza virus, wherein the equine influenza virus genome segment confers at least one identifying phenotype of the cold-adapted equine influenza virus, such as cold-adaptation, temperature sensitivity, dominant interference, or attenuation. Such viruses are formulated into therapeutic compositions to protect animals from diseases caused by influenza A viruses, and in particular, to protect horses from disease caused by equine influenza virus. The present invention also includes methods to protect animals from diseases caused by influenza A virus utilizing the claimed therapeutic compositions.

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: 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.

Abstract: The present invention relates to a composition and method for enhancing the efficacy of a vaccine in a subject treated with the vaccine by administering to the subject an antigen in conjunction with a chemokine.

Abstract: The present invention relates to a method for the adaptation of infectious bursal disease viruses (IBDV) to growth in CEF cell culture. Changing the codons for amino acid residues 253 (Gln) and 284 (Ala) to 253 (His) and 284 (Thr) allowed bursa adapted Classical and Variant-E IBDV to grow in CEF cell culture. For GLS IBDV only a change of the codon for amino acid residue 284 was necessary.

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: 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: The present invention relates to sub-unit vaccines comprising structural polypeptides of Infectious Pancreatic Necrosis Virus (IPNV) comprising structural proteins V2 and V3 folded as an empty IPNV viral capsid that approximates the size and structural conformation of native IPNV virus.

Abstract: A vaccine for the selective immunization of horses against EHV4 and/or EHV1 is provided comprising at least one of (i) EHV4 virus wherein a portion of the gG gene of the EHV4 virus that elicits a type-specific response to EHV4 has been deleted and (ii) EHV1 virus wherein a portion of the gG gene of the EHV1 virus that elicits a type-specific response to EHV1 has been deleted. Antibodies which specifically bind to a epitopes of EHV4 gG or EHV1 also are provided.

Abstract: A mutant virus for use as a vaccine, wherein the genome of the virus is defective in respect of a gene essential for the production of infectious virus. In one aspect the mutant virus is capable of protecting a susceptible species immunized therewith against infection by the corresponding wild-type virus. In another aspect, the mutant virus acts as a vector for an immunogenic protein derived from a pathogen and which is encoded by foreign DNA incorporated in the mutant virus. The mutant virus can be produced in a recombinant host cell which expresses a gene complementing the defect. The mutant virus is preferably infectious for the host to be protected, but the defective gene allows expression in the infected host of at least some of the viral genes, which can provoke a cell-mediated immune response.

Abstract: A method for producing a cellular immune response in a vertebrate subject comprising administering to the vertebrate subject a vaccine composition comprising a protein particle antigen and a pharmaceutically acceptable excipient is disclosed.

Abstract: The present invention is directed to a bacterial delivery system for delivering alphavirus replicon DNA into an animal or animal cells with the replicon encoding one or more heterologous genes to be expressed in the animal or the animal cells. The bacteria are invasive bacteria or attenuated invasive bacteria engineered to contain a DNA vector that encodes the alphavirus replicon in a eukaryotic expression cassette. The heterologous gene can encode an antigen, a therapeutic agent, an immunoregulatory agent, an anti-sense RNA, a catalytic RNA, a protein, a peptide, an antibody or an antigen-binding fragment of an antibody. In a preferred embodiment, the heterologous gene encodes one or more antigens useful as a vaccine for HIV. In addition to the bacterial delivery system, the invention provides methods of introducing and expressing the heterologous gene(s) in animal or animal cells and methods of stimulating or inducing an immune response.

Abstract: A method and system for determining the dominant cerebral hemisphere of a subject. There is further provided a method and system for using information obtained regarding hemisphere dominance for programming electronic devices such as robots, prostheses, as well as methods for using such information during treatment and surgical procedures in order to obtain superior function and/or movement when there is injury or disease to an area of the brain. A vectorial view of the role of callosum in the underpinning lateralities of speech and handedness, and as such, provides a technical definition of handedness (i.e., which hemisphere of the cerebrum is dominant in a particular individual subject). This technical definition is then used to completely accurately replicate or predict voluntary movements of the subject and this information, in turn, can be utilized in the field of prosthetics and robotics in order to obtain more accurate depiction of brain function and hence, more authentic replication of movement.

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: A promising approach for the therapeutic treatment of brain tumors utilizes replication-competent, neuroattenuated herpes simplex virus-1 (HSV-1) mutants. This approach requires mutation of HSV-1 to eliminate killing of normal, non-dividing cells of the brain (e.g., neurons). The present invention discloses methods for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the gamma 34.5 gene and the uracil DNA glycosylase (UNG) gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and is not neurovirulent.

Abstract: An innovative detection system for detecting small numbers of target analytes is disclosed. This system provides a novel method for attaching multiple copies of reporter groups to a single site on an analyte of interest. This system preferably comprises a virus capsid enclosing multiple detectable reporter groups, and a linking molecule which is capable of linking the capsid to the analyte of interest.

Abstract: The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Abstract: Isolated polynucleotide molecules provide RSV genome and antigenomes, including that of human, bovine or murine RSV or RSV-like viruses, and chimera thereof. The recombinant genome or antigenome can be expressed with a nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large (L) polymerase protein, and an RNA polymerase elongation factor to produce isolated infectious RSV particles. The recombinant RSV genome and antigenome can be modified to produce desired phenotypic changes, such as attenuated viruses for vaccine use.

Abstract: F gene-deficient virus virions are successfully recovered by using an f gene-deficient Sendai virus genomic cDNA. Further, F gene-deficient infectious viral particles are successfully constructed by using F-expressing cells as helper cells. Also, F gene and HN gene-deficient virus virions are successfully recovered by using a virus genomic cDNA deficient in both F gene and HN gene. Further, F gene and HN gene-deficient infectious viral particles are successfully produced by using F- and HN-expressing cells as helper cells. A virus deficient in F gene and HN gene and having F protein is constructed by using F-expressing cells as helper cells. In addition, M gene-deficient infectious virus particles were produced using helper cells expressing M protein. From cells infected with M gene-deficient viruses, release of virus-like particles was inhibited. Further, a VSV-G pseudo type virus is successfully constructed by using VSV-G-expressing cells.

Abstract: The present invention describes recombinant RV mutants comprising a combined mutation in two different parts of the viral genome, involving the P and the G genes. The mutations in the P gene preferably encompass residues 139 to 170, more preferably residues 139 to 149, most preferably residues 143-149. The mutation can be a substitution or deletion of one or more amino acids in the above region, as well as combinations of deletion and substitution.

Abstract: The present invention provides methods of expressing a nucleic acid or producing a proteinaceous composition encoded by a nucleic acid in vascular and cardiovascular cells by administration of a herpesvirus vector. The present invention provides methods of producing a therapeutic benefit in vascular and cardiovascular tissue by administration of a herpesvirus vector. In additional aspects, the invention concerns combination therapies for vascular and cardiovascular diseases comprising administration of a herpesvirus vector and treatment with at least one addition pharmacological agent or surgical procedure.

Abstract: Vaccine formulation comprising EHV-1 gene 71 dysfunctional mutant and uses thereof.

Abstract: The invention relates to antigenic preparations and vaccines directed against the porcine multisystemic wasting syndrome (PMWS), comprising at least one porcine circovirus antigen, preferably type II, and at least one porcine parvovirus antigen.

Abstract: Disclosed is a measles virus mutant antigen, comprising at least one protein antigen selected from the group consisting of (I) a measles virus mutant H protein antigen and (II) a measles virus mutant F protein antigen,

Abstract: Disclosed herein is a vaccine which provides immunity to mammals from infection and/or disease caused by a lentivirus, such as equine infectious anemia virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) or simian immunodeficiency virus (SIV) said composition comprising a deletion in a gene that blocks replication of the virus in vivo. Preferably said composition encompasses at least one deletion in a lentivirus which provides protection from exposure to wild-type lentiviruses. It also encompasses a marker vaccine in which a foreign gene is inserted into the gene-deleted region, said inserted gene providing a diagnostic tool for use in vaccinated mammals. The scope of the invention encompasses an EIAV vaccine that allows equines to be safely vaccinated and protected from disease without converting to a seropositive status on the Coggin's Test or any other test which measures p26.

Abstract: The present invention provides novel viral vectors. In one embodiment, the present invention provides mutant and recombinant bovine adenoviruses having a deletion and/or insertion of DNA in the early gene region 4 (E4). In another embodiment, the present invention provides mutant and recombinant bovine adenovirus 1 viruses having a deletion and/or insertion of DNA in the early gene region 3 (E3). The present invention also contemplates the use of the viral vectors for vaccination, gene therapy or other applications as suitable.

Abstract: The present invention relates to a treatment for animals having canine distemper by administering a composition comprising an attenuated canine distemper virus a sub-vaccine virus level effective to alleviate symptoms canine distemper. The invention also provides a treatment for animals having canine distemper by administering a composition comprising an attenuated canine measles virus a sub-vaccine virus level effective to alleviate symptoms canine distemper.