Abstract: The present invention relates to the production of vaccines having improved safety, particularly to a process therefor which allows even an AIDS vaccine to be manufactured, comprising in order, the steps of:a) treating the virus with a general inactivating agent;b) deaggregating the virus with a suitable solvent or detergent;c) treating the virus with an RNA and/or DNA inactivating agent; andd) stabilizing the virus with a suitable cross-linking agent.

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: Methods and compositions for treating pathogens in material are described, including methods of decontaminating human fluids prior to processing in the clinical laboratory and methods for decontaminating blood products prior to in vivo use. The techniques handle large volumes of human serum without impairing the testing results. Novel compounds for photodecontaminating biological material are also contemplated which are compatible with clinical testing, in that they do not interfere with serum analytes. In particular, quinacrine mustard is used to inactivate pathogens in red cell compositions with retention of red cell function.

Abstract: The present invention provides a live and inactivated Chicken Anaemia Agent vaccine capable of evoking an immune response in a vaccinated chicken. The CAA virus of the vaccine is attenuated by serial passages in embryonated eggs.

Abstract: Disclosed are oligonucleotides having nucleotide sequences that hybridize to at least nucleotides 324 to 348 of a conserved gag region of the HIV-1 genome. These oligonucleotides have about 25 to 30 nucleotides linked by at least one non-phosphodiester internucleotide linkage which render them resistant to nuclease digestion. Also disclosed are therapeutic formulations containing such oligonucleotides and methods of inhibition HIV-1 proliferation and of treating HIV-1 infection in a mammal.

Abstract: This invention relates to a reconstituted sendai-viral envelope containing the F-protein (F-virosomes) and to a process for producing a targeted gene or drug delivery carrier produced by the steps of chemical reduction of Sendai virus for reduction of HN protein and subjecting the reduced virus to the step of dialysis for removal of the reducing agent. The reduced virus is then solubilized with a detergent to obtain a solution. The said solution is centrifuged to separate the insolubles consisting of reduced HN protein and core of the virus, adding the required specific gene or drug to the centrifugal solution. Finally, the detergent is removed using an affinity complex agent which binds the detergent leading to the formation of the delivery carrier.

Abstract: The present invention provides a method for activating prothrombin to thrombin in a prothrombin complex composition comprising at least prothrombin, Factors V, VII, IX, and X, and phospholipid, comprising the steps of: (a) cold-incubating the prothrombin complex composition with 2-15 mM of Ca.sup.2+ ions at a pH of 6.5-8.0 and at a temperature of 2.degree.-8.degree. C. until Factor VII contained in the composition is activated; and (b) incubating the cold-incubated composition at a pH of 6.5-8.0 and at a temperature of 10.degree.-25.degree. C. for a period of time sufficient to activate prothrombin contained in the composition to thrombin.

Abstract: The present invention contemplates methods of decontaminating human fluids prior to processing in the clinical laboratory. The techniques handle large volumes of human serum without impairing the testing results. Novel compounds for photodecontaminating biological material are also contemplated which are compatible with clinical testing, in that they do not interfere with serum analytes.

Abstract: Method for inactivating non-enveloped viruses using a viricide-potentiating agent. In a preferred embodiment, the method may be used to inactivate non-enveloped viruses present within a sample of whole blood or a blood product and comprises (a) adding to the blood sample a photoactivatable viricide, such as a psoralen, hypericin, methylene blue, toluidine blue or the like, which, when activated, is effective in inactivating enveloped viruses; (b) adding to the blood sample a viricide-potentiating chemical agent that increases the sensitivity of non-enveloped viruses to the activated viricide; and (c) activating the photoactivatable viricide.

Abstract: In a method of producing a virus-safe biological preparation by heating while preserving a least 50% of its biologic activity, a biologially compatible tenside is added to the preparation before heating and heating is carried out in the presence of the same, whereupon the tenside, preferably, is eliminated.

Abstract: An improved process for inactivating an extracellular lipid enveloped virus or an intracellular lipid enveloped virus which may be present in an extracorporeal composition containing red blood cells by subjecting the composition to a virucidally effective amount of a phthalocyanine compound and red light of a fluence rate of at least above about 5 mW/cm.sup.2. Quite contrary to what would have been expected, it has been found that higher light fluence rates are, in fact, more protective of red blood cells than are lower light fluence rates.

Abstract: Disclosed are chemical agents with unexpected antimicrobial activity against the microbes, especially Porphyromonas gingivalis, known to be important in the cause and progression of gingivitis, periodontitis, and destruction of hard and soft oral tissues leading to tooth loss. The agents have additional unexpected anticollagenase activity useful in the direct mitigation of tissue damage. The agents can be formulated to produce various compositions and dental implements useful in management of peridental diseases, particularly those involving infection with certain gram-negative anaerobes.

Abstract: A method for the inactivation of prions, viruses and other infectious agents, which might be present in a biological raw material (e.g. plasma for the preparation of albumin), leaving the desired biological product (e.g. BSA, HSA) intact. To achieve this, the biological raw material is treated with a chaotropic agent, e.g. urea or siodium thiocyanate for approx. 18 hours. Before this, a detergent, e.g. sodium dodecyl sulfate, as well as ethanol or methanol can be added, and the solution can be heated to 70.degree. C. and kept at this temperature for 30 minutes. After cooling and acidification, denatured globulins can be removed. By modifications of this process (e.g. different concentrations, pH-values, temperatures etc.) a wide range of biological products (serum, plasma, proteins, peptides, gangliosides etc.) can be treated and rendered free of viruses, prions and all other infectivity.

Abstract: A method for template-dependent in vitro replication and transcapsidation of double stranded RNA from Reoviridae mRNA templates is described. This method provides an efficient means for isolating rotaviral mRNA, manipulating the mRNA, and expressing the new dsRNA species without the use of infected cells by constructing a new virus in the test tube without any cellular components. Viral protein complexes are prepared by test tube degradation of purified virus particles or by expression of a small subset of viral genes in insect cells, where the proteins form complexes. Viral mRNAs are made in the test tube by transcription of "native" viral mRNAs from viral transcriptase particles previously made in vitro, or by expression of viral mRNAs from transcription vectors in vitro.

Abstract: A safe, effective vaccine for the protection of susceptible animals against foot-and-mouth disease has been produced. The vaccine comprises a mutant virus from which the amino acid sequence Gly-Val-Arg-Gly-Asp-Phe (SEQ ID NO: 8) from the G-H loop of VP1 has been deleted and replaced with the amino acid sequence Asn-Pro. The mutant virus retains its antigenicity but is not infectious.

Abstract: The invention relates to methods and compositions for inhibition of viral replication. In particular, termination of replication of hepatitis B virus is achieved by introducing into a target cell an antisense oligonucleotide having a sequence substantially complementary to an mRNA which is in turn complementary to a portion of the minus strand of a hepatitis viral genome, which portion encoding solely part or all of the terminal protein region of the viral polymerase.

Abstract: Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.

Abstract: A method of producing infectious bursal disease virus comprising culturing infectious bursal disease virus in a mammalian cell line for two to ten days.

Abstract: The present invention provides a method for inactivating pathogens in a body fluid, such as plasma, red cells, platelets, leukocytes, and bone marrow. The present invention minimizes adverse effects caused by the photosensitive agents while retaining the disinfecting activity of such agents and processes. Pursuant to the present invention, prior to irradiating a body fluid including a photoactive drug, the extracellular fluid, which in the case of blood components includes plasma proteins is at least substantially reduced. Additionally, after the irradiation process, the resultant body fluid is prevented from contacting additional extracellular fluid, e.g., plasma proteins, for a predefined period.

Abstract: Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.

Abstract: Non-peptide, protease-binding compounds are described as useful in the detection, labelling, and inhibition of retroviral proteases. Aryl piperidinyl derivatives and other compounds related in structure have been found to be HIV-1 and HIV-2 protease-binding compounds.

Abstract: A method for using thiazine dyes, especially methylene blue, alone or in combination with low levels of light, to selectively inactivate or inhibit intracellular replication of specific viruses, especially human immunodeficiency virus in vitro and in vivo. Examples of useful thiazine dyes are methylene blue, azure A, azure C, toluidine blue O, and thionine. The preferred dye at this time is methylene blue. Methylene blue is FDA approved for topical, i.v., and oral administration, and has minimal side effects. Since methylene blue absorbs in the red wavelengths, i.e., approximately 670 nm, which penetrates tissue much better than other lower wavelengths, light penetrating the skin to the capillaries at the surface can be used to enhance the activity of the dye.

Abstract: A method and compositions for treating viral infection in vitro and in vivo using a guanosine-rich oligonucleotides. The oligonucleotides are composed of at least about 50% guanosine nucleotides. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity.

Abstract: A new method of inactivating enveloped viruses and preparations useful in accomplishing this inactivation are disclosed. The method is based on the discovery that paucilamellar lipid vesicles, preferably having non-phospholipids as their primary structural material, can fuse with enveloped virus and that the nucleic acid of the virus denatures shortly after the fusion. The method is useful for inactivating viruses such as orthomyxoviruses, paramyxoviruses, coronaviruses, and retroviruses.

Abstract: The invention relates to hepatitis A viruses (HAVs) having a serotype displaying the immunological characteristics of the HAV strain RG-SB XA112 (CNCM I-1080). In particular, the invention relates to the new hepatitis A virus strain RG-SB XA112 (CNCM I-1080). The invention also relates to structural components of said HAVs. Furthermore, the invention relates to processes for the isolation of said HAVs. The HAVs of the present invention and the structural components thereof can be used for the production of vaccines and diagnostic compositions. Finally, the invention relates to polyclonal and monoclonal antibodies which are directed to said new HAVs.

Abstract: Disclosed are oligonucleotides complementary to and hybridizable with a portion of the BZLF1 RNA of Epstein-Barr virus, useful for inhibiting the induction of the lytic cycle in EBV-infected cells, and in inhibiting EBV replication.

Abstract: Monofucosylated and monosialyated derivatives of the compound .beta.Gal(1-4).beta.GlcNAc(1-3).beta.Gal(1-4).beta.GlcNAc-OR, where R is hydrogen, a saccharide, an oligosaccharide or an aglycon moiety have been found to be useful in modulating a cell-mediated immune inflammatory response in mammals.

Abstract: A new virus not neutralized or bound by monoclonal antibodies which are group neutralizing to all IBDV vaccines of current art, and capable of inducing infectious bursal disease in poultry is identified, in essentially pure form. A test kit, and assay for the presence of the virus is disclosed, together with the vaccine incorporating the virus. A monoclonal antibody Mab 50, which neutralizes the virus, form the basis of an alternative vaccine.

Abstract: Compositions and methods are provided for the treatment and diagnosis of herpesvirus infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with RNA or DNA deriving from a herpesvirus gene corresponding to one of the open reading frames UL5, UL8, UL9, UL20, UL27, UL29, UL30, UL42, UL52 and IE175 of herpes simplex virus type 1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a translation initiation site, a coding region or a 5'-untranslated region. Methods of treating animals suspected of being infected with herpesvirus comprising contacting the animal with an oligonucleotide of the invention are disclosed.

Abstract: This invention is directed to the sterilization of collagen and collagenous tissue which is to be used for implantation, repair, or use in a mammalian host in the emerging field of tissue engineering. The sterilants are low concentration peracetic acid solutions in either neutral or high ionic strength that prevent or minimizes the swelling of collagen or collagenous tissue so that the sterilized tissue retains its structural integrity and bioremodelable properties.

Abstract: This invention relates to a method and composition for inhibiting or destroying viruses or retroviruses in a mammalian host. The method comprises contacting the viruses or retroviruses with a composition. The composition comprises an active ingredient capable of inhibiting or destroying viruses or retroviruses, for example, a surfactant, and an activating ingredient capable of inhibiting or destroying one or more enzymes associated with viruses or retroviruses, for example, a fluorinated compound capable of releasing fluoride anions, and an excipient.

Abstract: Embryonal vaccination of fowl against Newcastle disease is accomplished with ethyl methane sulfonate modified NDV-B1 virus.

Abstract: The present invention provides a biologically pure culture of a novel pathogenic porcine respiratory coronavirus (PRCV) and a vaccine derived therefrom effective against PRCV infection and transmissible gastroenteritis virus (TGEV) infection.

Abstract: A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers and irradiated with, for example, UV, visible, gamma or X-ray radiation. In particular, quaternary ammonium or phosphonium substituted, halo-psoralen compounds are described as being useful.

Abstract: Disclosed are methods for the preparation of monofucosylated and sialylated derivatives of the compound .beta.Gal(1-4).beta.GlcNAc(1-3).beta.Gal(1-4).beta.GlcNAc-OR. In particular, the methods of this invention provide for a multi-step synthesis wherein selective monofucosylation is accomplished on the 3-hydroxy group on only one of the GlcNAc units found in the .beta.Gal(1-4) .beta.GlcNAc (1-3) .beta.Gal (1-4) .beta.GlcNAc-OR compound. In this step, monofucosylation is achieved by use of the .alpha.(1-3)fucosyltransferase.

Abstract: A multivalent FeLV-infected feline vaccine composed of (1) a small but immunologically effective amount of inactivated feline leukemia virus; (2) a small but effective amount of an inactivated virus selected from the group consisting of Feline Rhinotracheitis Virus, Feline Calici Virus and Feline Panleukopenia Virus; and (3) a pharmaceutically acceptable immunologica adjuvant. Components (1) and (2) may be inactivated by any of the known techniques. The inactivated feline leukemia virus must be from subgroup A and is the Rickard isolate of the virus designated FeLV-A.sub.R1. This combination vaccine is effective in preventing Viremia, leukemia-associated syndromes, and deaths in cats caused by Feline Leukemia Virus, Feline Rhinotracheitis Virus, Feline Calici Virus and Feline Panleukemia Virus infections.

Abstract: The present invention provides a method for inactivating pathogens in a body fluid, such as plasma, red cells, platelets, leukocytes, and bone marrow. The present invention minimizes adverse effects caused by the photosensitive agents while retaining the disinfecting activity of such agents and processes. Pursuant to the present invention, prior to irradiating a body fluid including a photoactive drug, the extracellular fluid, which in the case of blood components includes plasma proteins is at least substantially reduced. Additionally, after the irradiation process, the resultant body fluid is prevented from contacting additional extracellular fluid, e.g., plasma proteins, for a predefined period.

Abstract: The present invention concerns a vaccine comprising a novel canine parvovirus strain and having the property of being able to break through the maternally derived antibody levels persistent in 9-12 week old pups, and even to immunize the majority of pups at the age of 6 weeks in the presence of maternally derived antibodies.

Abstract: The present invention provides compounds that function as hydrolytic enzyme inhibitors (inactivators) and substrates. These compounds are useful in assays to detect and measure levels of hydrolytic enzyme activity and are more particularly useful in treatment regimens for various disease states and conditions implicating the underlying specific hydrolytic enzyme. Examples of hydrolytic enzymes include, but are not limited to, phospholipases, lipases, esterases, proteases, etc.

Abstract: The present invention provides a fail-safe combination of chemical and physical means for rendering a blood product which comprises a labile blood protein free of viruses without incurring protein denaturation. The blood product is contacted with an effective amount of a selected chemical disinfectant, preferably, sodium thiocyanate in combination with a physical process, preferably, ultrafiltration. The blood product may be plasma, serum, plasma concentrate, cryoprecipitate, cryosupernatant, plasma fractionation precipitate or plasma fractionation supernatant containing viruses such as hepatitis or human immunodeficiency virus.

Abstract: Type-C rotavirus are propagated in swine testicular cells with reduced concentrations of proteolytic enzyme for subsequent production of antigen and antiserum for use in diagnostic kits and for killed vaccines to prevent Type C rotavirus infections. Propagation of Type C rotavirus in the ST cells can also lead to virus modification for subsequent use as a modified live virus vaccine to prevent Type C rotavirus infections.

Abstract: The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.

Abstract: A live or inactivated canine corona virus vaccine is provided which is derived from a virus of the novel antigenic type of the canine corona virus strain I-743 (CNCM, Institut Pasteur, Paris). A method for the preparation of this vaccine and the use of said vaccine in protecting susceptible animals against canine corona virus injection are also disclosed.

Abstract: A vaccine against a herpes virus is prepared by infecting cells with virus, separating the nuclei of the infected cells from their cytoplasmic fraction, discarding the nuclei, fixing the polypeptide chains of the virus antigens in the cytoplasmic fraction, and precipitating those antigens, the precipitated antigens providing the active constituent of the vaccine. A characteristic strain of the virus may be used, so that vaccinated subjects can be distinguished from infected subject.

Abstract: The present invention provides an inactivated encephalomyocarditis virus (EMCV) vaccine produced from swine isolates which protects swine from diseases caused by EMCV. The vaccine is produced from swine isolates and protects against respiratory problems, myocardial and pulmonary inflammation and necrosis, and confers protection against reproductive disorders resulting from some strains of the virus.

Abstract: Disclosed is a novel biological system for 1) the evaluation of potential complications of live virus vaccines prior to actual testing in animals or in the field, and 2) the construction of vaccine vectors in which the ability to grow within specific organs or tissues has selectively been eliminated from the virus.

Abstract: The present invention relates to Hantaan virus and a vaccine therefor. The Hantaan virus vaccine can be prepared as follows: The Hantaan virus ROK84/105 strain isolated from the human body as a seed strain, injected to one-day-old suckling mouse or rat, which is raised for about 10 days. Thereafter, the head of the mouse or rat is cut apart after paralyzing the mouse or rat to take the brain, the brain is treated with ethyl alcohol and protamine sulfate solution, the resultant is purified and inactivated, and an adjuvant is added to the final product.

Abstract: A strain of influenza virus, especially human influenza type A or B, for use in formulating a vaccine is selected by a process which comprises isolating candidate influenza viruses in embryonated hens' eggs, determining whether they have antigenic similarities to strains which are the same except that they have been isolated and grown exclusively in animal cells, that is to say whether they are "cell-like", and selecting at least one such cell-like strain or a reassortant thereof having its HA and NA genes for the vaccine.

Abstract: Type-C rotavirus are propagated in swine testicular cells with reduced concentrations of proteolytic enzyme for subsequent production of antigen and antiserum for use in diagnostic kits and for killed vaccines to prevent Type C rotavirus infections. Propagation of Type C rotavirus in the ST cells can also lead to virus modification for subsequent use as a modified live virus vaccine to prevent Type C rotavirus infections.

Abstract: Vaccines employing inactivated viruses having improved retention of antigenic characteristics are prepared by psoralen-inactivation of the live virus in a non-oxidizing atmosphere. By excluding oxygen and other oxidizing species from the inactivation medium, degradation of the antigen characteristics resulting from irradiation with ultraviolet light is largely prevented. The resulting inactivated viruses are employed in vaccine preparations for the inoculation of susceptible hosts to inhibit viral infection.