Abstract: The invention provides methods of preventing and treating flavivirus infection in animals.

Abstract: The present invention is related to a vaccine composition for humans against YF infections consisting essencially of a recombinant YF virus, YFiv5.2/DD, which is regenerated from YF infectious cDNA. There is provided new plasmids, pYF 5′3′ IV/G1/2 and pYFM 5.2/T3/27, which together, have the complete sequence of said YF infectious cDNA. The method for producing recombinant YF virus and the Original, Primary and Secondary Seed Lots are other embodiments of the present invention.

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: This invention is directed to antigen library immunization, which provides methods for obtaining antigens having improved properties for therapeutic and other uses. The methods are useful for obtaining improved antigens that can induce an immune response against pathogens, cancer, and other conditions, as well as antigens that are effective in modulating allergy, inflammatory and autoimmune diseases.

Abstract: An adenovirus which encodes a polypeptide which produces a protective immune response against an alpha-virus such as a Venezuelan Equine Encephalitis Virus, in a mammal to which it is administered, said nucleic acid lacking a competant nuclear targeting signal in the capsid gene.

Abstract: The present invention provides a safe and effective vaccine composition against West Nile virus disease. An immunogenically active component of West Nile virus or plasmid DNA, an adjuvant such as a metabolizable oil, and a pharmacologically acceptable carrier are formulated into an immunizing vaccine. The invention also provides a method for the prevention or amelioration of West Nile disease, such as encephalitis, in equidae by administering the vaccine composition herein set forth.

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

Abstract: 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: This invention is directed to antigen library immunization, which provides methods for obtaining antigens having improved properties for therapeutic and other uses. The methods are useful for obtaining improved antigens that can induce an immune response against pathogens, cancer, and other conditions, as well as antigens that are effective in modulating allergy, inflammatory and autoimmune diseases.

Abstract: The present invention provides a helper cell for expressing an infectious, replication defective, alphavirus particle in an alphavirus-permissive cell. The helper cell includes (a) a first helper RNA encoding (i) at least one alphavirus structural protein, and (ii) not encoding at least one alphavirus structural protein; and (b) a second helper RNA separate from the first helper RNA, the second helper RNA (i) not encoding the alphavirus structural protein encoded by the first helper RNA, and (ii) encoding the at least one alphavirus structural protein not encoded by the first helper RNA. Preferably, the helper cell is co-transfected with a replicon RNA encoding an alphavirus packaging segment and an inserted heterogeneous RNA, such that all of the alphavirus structural proteins assemble together into alphavirus particles in the cell, with said replicon RNA packaged therein.

Abstract: The present invention provides vaccine compositions of attenuated dengue-4 virus. More specifically, the attenuated virus is produced by serial passage in PDK cells. The invention also provides methods for stimulating the immune system of an individual to induce protection against dengue-4 virus by administration of attenuated dengue-4 virus.

Abstract: The present invention provides a helper cell for expressing an infectious, replication defective, alphavirus particle in an alphavirus-permissive cell. The helper cell includes (a) a first helper RNA encoding (i) at least one alphavirus structural protein, and (ii) not encoding at least one alphavirus structural protein; and (b) a second helper RNA separate from the first helper RNA, the second helper RNA (i) not encoding the alphavirus structural protein encoded by the first helper RNA, and (ii) encoding the at least alphavirus one structural protein not encoded by the first helper RNA, such that all of the alphavirus structural proteins assemble together into alphavirus particles in the cell. Preferably, the helper cell also includes a replicon RNA encoding an alphavirus packaging sequence and an inserted heterogeneous RNA.

Abstract: The present invention provides immunogenic compositions of attenuated dengue-1 virus. More specifically, the attenuated virus is produced by serial passage in PDK cells. The invention also provides methods for stimulating the immune system of an individual to induce protection against dengue-1 virus by administration of attenuated dengue-1 virus.

Abstract: An improved method of inducing whole-body hyperthermia and enhanced anti-tumor immune response through inoculation of a fever virus with nil mortality and subsequent injection of irradiated tumor cells derived from the patient. This therapy will safely reduce the tumor burden by 90-99.9% by physical means (fever), before raising interferon levels to over 250 times baseline. The Activated Lymphokine Killer cells produced by these high interferon levels are capable of killing any cell expressing viral or tumor antigens, even those which had previously escaped immune surveillance. As a final step in the process, a specific class of Cytotoxic T Lymphocytes programmed to destroy the patient's own cancer cells will be produced by repeated inoculation of irradiated cancer cells harvested from the patient.

Abstract: The present invention provides a helper cell for expressing an infectious, replication defective, alphavirus particle in an alphavirus-permissive cell. The helper cell includes (a) a first helper RNA encoding (i) at least one alphavirus structural protein, and (ii) not encoding at least one alphavirus structural protein; and (b) a second helper RNA separate from the first helper RNA, the second helper RNA (i) not encoding the alphavirus structural protein encoded by the first helper RNA, and (ii) encoding the at least one alphavirus structural protein not encoded by the first helper RNA. Preferably, the helper cell is co-transfected with a replicon RNA encoding an alphavirus packaging segment and an inserted heterogeneous RNA, such that all of the alphavirus structural proteins assemble together into alphavirus particles in the cell, with said replicon RNA packaged therein.

Abstract: A recombinant protein encompassing the complete envelope glycoprotein and a portion of the carboxy-terminus of the membrane/premembrane protein of dengue 2 virus was expressed in baculovirus as a protein particle. The recombinant protein particle was purified and found to provide protection against lethal challenge with dengue 2 virus in mice.

Abstract: The present invention encompasses isolated nucleic acids containing transcriptional units which encode a signal sequence of one flavivirus and an immunogenic flavivirus antigen of a second flavivirus. The invention further encompasses a nucleic acid and protein vaccine and the use of the vaccine to immunize a subject against flavivirus infection. The invention also provides antigens encoded by nucleic acids of the invention, antibodies elicited in response to the antigens and use of the antigens and/or antibodies in detecting flavivirus or diagnosing flavivirus infection.

Abstract: The present invention provides vaccine compositions of attenuated dengue-2 virus. More specifically, the attenuated virus is produced by serial passage in PDK cells. The invention also provides methods for stimulating the immune system of an individual to induce protection against dengue-2 virus by administration of attenuated dengue-2 virus.

Abstract: What is described is a recombinant poxvirus, such as avipox virus, containing foreign DNA from porcine circovirus 2. What are also described are immunological compositions containing the recombinant poxvirus for inducing an immunological response in a host animal to which the immunological composition is administered. Also described are methods of treating or preventing disease caused by porcine circovirus 2 by administering the immunological compositions of the invention to an animal in need of treatment or susceptible to infection by porcine circovirus 2.

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: This invention provides a Togavirus-amplified retrovirus vector and a novel method for packaging a retrovirus cassette that contains a heterologous nucleic acid, which is amplified in a packaging cell cytoplasm by a Togavirus vector. The retroviral cassette is packaged into infectious retrovirus particles by retroviral packaging cells. These retroviral particles carrying the retroviral packaging cassette are then used to infect host cells.

Abstract: The present invention provides a purified preparation containing, for example, at least one polypeptide selected from the group consisting of proteins encoded by one or more open reading frames (ORF's) of an Iowa strain of porcine reproductive and respiratory syndrome virus (PRRSV), antigenic regions of such proteins which are at least 5 amino acids in length and which effectively protect a porcine host against a subsequent challenge with a PRRSV isolate, and combinations thereof in which amino acids non-essential for antigenicity may be conservatively substituted. The present invention also concerns a vaccine comprising an effective amount of such a protein; antibodies which specifically bind to such a protein; methods of producing the same; and methods of protecting a pig against a PRRSV, treating a pig infected by a PRRSV, and detecting PRRSV in a pig.

Abstract: A vaccine for promoting an immune response in a mammalian subject includes a eucaryotic plasmid expression vector which include at least part of the envelope gene and optionally, the PreM gene of dengue virus. In order to minimize immune enhancement, vaccines of up to the four serotypes of dengue are combined in a single vaccine. The vaccine in a suitable pharmaceutical carrier constitutes a pharmaceutical composition which is injected into the subject.

Abstract: A vaccine contains at least one Drosophila cell-secreted, recombinantly-produced form of a truncated Flavivirus envelope glycoprotein, as an active ingredient, and an adjuvant, as a critical component of the vaccine. The adjuvant is an immunomodulating agent having an iscom-like structure and comprising within the iscom-like structure at least one lipid and at least one saponin, and a pharmaceutically acceptable vehicle. Such a vaccine protects a subject against infection by a Flavivirus.

Abstract: The invention involves viral vectors that can be used to transduce a target cell, i.e., to introduce genetic material into the cell. The targets of interest are eukaryotic cells and particularly human cells. The transduction can be done in vivo or in vitro. More particularly the invention concerns viral vectors that have chimeric envelope proteins and contain the IgG-binding domain of protein A. These vectors when used in conjunction with antibodies targeting a particular cell are particularly useful for gene therapy.

Abstract: The present invention is directed to genetically engineered, membrane-enveloped viruses with deletion mutations in the protein transmembrane domains. Also provided are viral vaccines based on the engineered viruses, methods of producing and using such vaccines.

Abstract: A vaccine comprises a non-cytopathogenic strain of bovine viral diarrhea virus, grown in a bovine derived cell line such as MDBK and killed, for example with &bgr;-propiolactone. The adjuvant is Quil A.

Abstract: The recombinant expression and secretion from eucaryotic host cells, particularly Drosophila cells, of Flavivirus nonstructural (NS) protein, particularly NS1, is useful in combination with Flavivirus truncated envelope (E) protein to protect a host subject from infection and disease from Flavivirus species. Further, NS1 is useful as a diagnostic of flaviviral infection. Compositions of truncated flaviviral envelope protein and flaviviral nonstructural protein induce high titer virus neutralizing antibodies believed to be important in protection against flaviviral infection and which are useful in diagnosis of infection by the virus.

Abstract: The present invention is directed to a method of producing attenuated forms of bovine viral diarrhea (BVD) virus by mutating the Npro protease gene. The invention includes the attenuated viruses made by this method, antibodies generated using these viruses, and vaccines that can be used for immunizing cattle.

Abstract: The present invention is directed to a method of producing attenuated forms of bovine viral diarrhea (BVD) virus by mutating the Npro protease gene. The invention includes the attenuated viruses made by the method, antibodies generated using these viruses, and vaccines that can be used for immunizing cattle.

Abstract: Porcine reproductive and respiratory syndrome (PRRS), which has also been termed mystery swine disease, swine infertility and respiratory syndrome (SIRS), and porcine epidemic abortion and respiratory syndrome (PEARS), induces severe disease in pigs and causes considerable economic loss to farmers. The pathology of PRRS is characterized by severe reproductive failure in sows, mild to severe respiratory distress, increased mortality in weaning pigs, conjunctivitis, and lymphnode enlargement. The pathogen responsible for PRRS is an enveloped RNA virus belonging to the Arterivirus group within the Togaviridae family. The PRRS viruses are single stranded RNA viruses having a viral genome of positive polarity and a size of approximately 15 kb. The positive-strand RNA genome possesses at least three major structural proteins designated N, M, and E. The PRRS viruses exist as a quasispecies and display considerable genotypic and phenotypic heterogeneity.

Abstract: This invention relates to hepatitis B virus (“HBV”) core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them.

Abstract: The present invention relates to five synthetic peptides of pre-M/M protein of Dengue-2 virus, corresponding to amino acid sequences 3-31, 45-67, 57-92, 69-93 and 103-124. The anti-peptide immune response was evaluated in mice. Recombinant fusion proteins were also obtained, including regions of pre-M/M protein. The presence of B cell epitopes in both mice and humans was demonstrated in the pre-M/M protein peptides. Peptides 3-31 and 103-124 elicited neutralizing antibodies against the four serotypes of Dengue virus. Virus-specific proliferative responses were demonstrated in mice immunized with non-conjugated peptides 3-31 and 57-92. Mice immunized with conjugated peptides 3-31, 57-92, and 69-93 were protected when they were challenged with Dengue-2 virus. Thus, the presence of sequential epitopes in Pre-M/M protein of Dengue-2 virus was demonstrated, as well as their relevance in the immune response against this flavivirus.

Abstract: The invention concerns an immunogenic construct comprising as components (i) an inactive flavivirus or a derivative thereof, and (ii) at least one immunogenic component which is bonded to the flavivirus or adsorbed therewith. The invention further concerns a process for preparing the immunogenic construct and its use as a vaccine.

Abstract: The invention encompasses methods and compositions for inducing an immune response in an anti-Gal synthesizing animal including viral and tumor antigens manipulated to express &agr;-galactosyl epitopes.

Abstract: Methods of production and purification for viruses and virus-derived vectors, including those related to alphaviruses, are disclosed. In one aspect, methods of purification that subject alphavirus replicon particle preparations to one or more steps of chromatographic purification, such as using an ion exchange resin, are provided. Also disclosed are methods of characterizing alphavirus replicon particles and utilizing these materials for vaccines and gene-based therapeutics.

Abstract: A peptide or peptide conjugate is provided comprising one or more epitopes capable of producing an immune response against equine arteritis virus in animals. The peptides and conjugates are useful in vaccines directed against equine arteritis virus, an agent implicated in equine abortion, and as binding agents for use in binding assays, including ELISA assays, for antibodies thereto. Antibodies and antisera to the peptides and peptide conjugates may also be used as such binding agents in assays directed at the virus itself.

Abstract: The invention relates to vaccine preparations, pharmaceutical preparations and methods for inducing protective immunity in humans using a live, attenuated yellow fever virus of strain D17 preferably administered by an intranasal route of administration. The inventors have also developed an assay for detecting the induction of both the binding and neutralizing antibodies formed in a protective immune response in humans who have received an intranasal vaccine preparation of the kind described.

Abstract: An attenuated Japanese encephalitis virus adapted to Vero cell by passages on Vero cell is disclosed. A Japanese encephalitis vaccine comprising said attenuated virus is also disclosed.

Abstract: The vaccines and methods of the present invention are based on deletion mutations in the protein transmembrane domains of membrane-enveloped viruses. 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; thus are 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. Provided is a vaccine, a method of producing this vaccine, and a method of using this vaccine, based on the differences between membranes of viruses replicated in invertebrates and membranes of viruses replicated in vertebrates.

Abstract: A live attenuated Venezuelan equine encephalitis virus (VEE) is described which comprises a viral gene rearrangement. This rearranged attenuated virus is useful as vaccine for protection against infection with VEE. Methods of preparing the virus and methods of using the virus are described.

Abstract: A vaccine comprises a non-cytopathogenic strain of bovine viral diarrhoea virus, grown in a bovine derived cell line such as MDBK and killed, for example with &bgr;-propiolactone. The adjuvant is Quil A.

Abstract: In this application is described a method for overcoming alphavirus vaccine interference in alphavirus-immune subjects by administration of a second alphavirus vaccine which is altered such that it is not accessible to interfering antibodies. Examples of such alterations are described as well as evidence showing that alphavirus interference likely results from the binding of interfering antibodies to viral proteins expressed on infected cells thereby causing lysis of infected cells.

Abstract: cDNAs coding for an infectious Western Equine Encephalitis virus (WEE) and infectious Venezuelan Equine Encephalitis virus variant IE (VEE IE) are disclosed in addition to cDNA coding for the structural proteins of Venezuelan Equine Encephalitis virus variant IIIA (VEE IIIA). Novel attenuating mutations of WEE and VEE IE and their uses are described. Also disclosed are attenuated chimearic alphaviruses and their uses.

Abstract: Particle mediated immunization of tick-borne flavivirus genes confers homologous and heterologous protection against tick borne encephalitis.

Abstract: An inactivated dengue virus vaccine to immunize and protect humans against dengue fever is described. The vaccine is based on dengue viruses which have been propagated to high titers in suitable cells, purified and inactivated under conditions which destroy infectivity but preserve immunogenicity, a high level of which is demonstrated in animal models.

Abstract: The present invention provides a vaccine which protects pigs from a virus and/or an infectious agent causing a porcine respiratory and reproductive disease, a method of protecting a pig from a disease caused by a virus and/or an infectious agent which causes a respiratory and reproductive disease, a method of producing a vaccine against a virus and/or an infectious agent causing a porcine reproductive and respiratory disease, and a biologically pure sample of a virus and/or infectious agent associated with a porcine respiratory and reproductive disease, particularly the Iowa strain of porcine reproductive and respiratory syndrome virus (PRRSV), and an isolated polynucleotide which is at least 90% homologous with a polynucleotide obtained from the genome of a virus and/or infectious agent which causes a porcine respiratory and reproductive disease.

Abstract: The present invention provides a purified preparation containing, for example, a polynucleic acid encoding at least one polypeptide selected from the group consisting of proteins encoded by one or more open reading frames (ORF's) of an Iowa strain of porcine reproductive and respiratory syndrome virus (PRRSV), antigenic regions of such proteins which are at least 5 amino acids in length and which effectively protect a porcine host against a subsequent challenge with a PRRSV isolate, and combinations thereof in which amino acids non-essential for antigenicity may be conservatively substituted. The present invention also concerns a polypeptide encoded by such a polynucleic acid; a vaccine comprising an effective amount of such a polynucleic acid or protein; antibodies which specifically bind to such a polynucleic acid or protein; methods of producing the same; and methods of protecting a pig against a PRRSV and treating a pig infected by a PRRSV.

Abstract: The present invention is directed to alphavirus expression vectors comprising at least part of an alphavirus genome and heterologous RNA inserted downstream of an alphavirus base sequence having translation enhancing activity. Such vectors can be used to achieve enhanced levels of expression of DNA or cDNA coding for a desired product and being complementary to said heterologous RNA after introduction of said vector in eukaryotic cells in cell culture or in a living body. The expression product may have therapeutical or prophylactic activity.

Abstract: This invention provides a process for large-scale purification of living Japanese encephalitis virus (JEV) suitable for use in vaccine preparation from a JEV source, including a JEV-infected cell culture and a JEV-infected mouse brain. The process includes the following steps: (a) obtaining a sample from a JEV-infected mouse brain or a JEV-infected cell culture, (b) subjecting the sample to a preliminary separation to remove cell and cell debris from the sample of step (a), (c) concentrating the sample from step (b) by ultra-filtration to remove substances having molecular weight below 100 kDa, and (d) subjecting the sample concentrate to gel filtration to obtain a substantially pure fraction of JEV.