152 results about "Alphavirus" patented technology

A vector comprising a first DNA sequence which is complementary to at least part of an alphavirus RNA genome and having the complement of complete alphavirus DNA genome replication regions, a second DNA sequence encoding a paramyxovirus protein, particularly a respiratory syncytial virus fusion (RSV F) protein or a RSV F protein fragment that generates antibodies that specifically react with RSV F protein, the first and second DNA sequences being under the transcriptional control of a promoter is described. Such vector may be used to produce an RNA transcript which may be used to immunize a host, including a human host, to protect the host against disease caused by paramyxovirus, particularly respiratory syncytial virus, by administration to the host.

The invention features compositions and methods for the prevention or treatment of one or more strains of Chikungunya virus, as well as other alphavirus-mediated diseases.

The present invention provides a recombinant nucleic acid comprising: a first nucleic acid sequence encoding a 5′ alphavirus replication recognition sequence; at least one second nucleic acid sequence encoding an alphavirus nonstructural protein; at least one alphavirus subgenomic promoter; at least one IRES element; at least one heterologous nucleic acid; and a third nucleic acid encoding a 3′ alphavirus replication recognition sequence. Further provided are methods of making alphavirus particles comprising a recombinant nucleic acid of this invention and methods of using the compositions of this invention. Also provided is a recombinant helper nucleic acid comprising: a first nucleic acid sequence encoding a 5′ alphavirus replication recognition sequence; an alphavirus subgenomic promoter; an IRES element; a second nucleic acid encoding an alphavirus structural protein; and a third nucleic acid encoding a 3′ alphavirus replication recognition sequence.

The technology is a veterinary pharmaceutical formulation of two vaccines, one from an RNA viral vector system constituted by an RNA recombinant particle that codifies for a Cu/Zn superoxide dismutase protein of Brucella abortus, and the other based on naked RNA constituted by a recombinant molecule of naked RNA that carries a sequence for the synthesis of at least one recombinant Cu/Zn superoxide dismutase protein of Brucella abortus and some Semliki Forest virus genes. An expression system based on the Semliki Forest virus and a use of this system, in addition to a method for the preparation of the pharmaceutical formulations.

Nucleic acid molecules and vector platforms derived from human virus vaccines, for example the alphavirus vaccines, including the TC-83 human vaccine, are disclosed. These vector platforms can provide for expression of a heterologous protein or nucleic acid in animal or human cells. In preferred embodiments, the nucleic acid molecules and vector platforms can be safely used to make and administer vaccines or gene therapies.

The present invention concerns recombinant DNA's comprising cDNA of genomic RNA of a Salmonidae alphavirus preceded by a spacer sequence, under the control of a suitable promoter. Said recombinant DNA's are useful for obtaining expression vectors, producing recombinant Salmonidae alphavirus, and for obtaining vaccines.

Chimeric alphaviruses and alphavirus replicon particles are provided including methods of making and using same. Specifically, alphavirus particles are provided having nucleic acid molecules derived from one or more alphaviruses and structural proteins (capsid and/or envelope) from at least two or more alphaviruses. Methods of making, using, and therapeutic preparations containing the chimeric alphavirus particle, are disclosed.

Provided herein are alphavirus vectors derived from South African Arbovirus No. 86 (S.A.AR86) comprising attenuating mutations and methods of making the same. Also provided are improved viral vectors and helper constructs comprising a S.A.AR86 capsid enhancer sequence. The present invention also provides S.A.AR86 replicon and helper constructs comprising an alphavirus capsid enhancer sequence. Further provided are methods of administering an alphavirus vector comprising a heterologous nucleotide sequence (preferably encoding an immunogen or a therapeutic polypeptide) according to the invention to a cell or subject. In preferred embodiments, the alphavirus vector delivers the heterologous nucleotide sequence to the cells of the bone, bone marrow, and/or bone-associated connective tissue.

The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with SS or SA hemoglobin or erythroleukemia cells stably transfected with BCAM/Lu which are capable of selectively localizing in tumor vasculature promoting ischemia and occlusion and carrying oncolytic viruses, antitumor proteins, plasmids, toxins and chemotherapy into the tumor milieu. Nucleated erythroid precursors containing SS or SA hemoglobin and transfected with nucleic acids encoding a hypoxia-responsive element and containing nucleic acids encoding expression of oncolytic viruses, superantigens, toxins, viruses, antitumor proteins and chemotherapy are also useful in inducing a potent and specific tumoricidal response. An especially favored carrier is an SS nucleated erythroid precursor transfected with a replication competent oncolytic adenovirus or self-replicating alphavirus expressing a fusogenic membrane glycoprotein or a tumoricidal polypeptide.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

The present invention relates to methods and compositions for treating tumors using vectors that preferentially target tumor cells. In particular, the invention relates to Sindbis virus vectors which have a preferential affinity for high affinity laminin receptors (HALR). These vectors are efficiently targeted to tumors and have the ability to cause tumor necrosis.

The present invention provides immunogenic compositions and methods that may be used to administer safer (i.e., attenuated) alphavirus vectors (such as alphavirus vectors comprising a VEE virion shell) that retain improved immunogenicity as compared with other attenuated alphaviruses (e.g., the VEE 3014 mutant, described below). In particular embodiments of the invention, the alphavirus vector comprises VEE structural proteins comprising an attenuating mutation in the E1 glycoprotein. In other particular embodiments, the attenuating mutation is in the fusogenic region of the E1 glycoprotein. The present invention enables administration of lower dosages of a safer (i.e., attenuated) virus and, thus, can further reduce manufacturing costs. The present inventors have found that immunogenicity of alphavirus vectors may be influenced by a number of factors including species, site and route of administration.

The present invention provides an avian cell that is derived from an avian host cell and stably carries at least one DNA sequence in the cell nucleus encoding an alphavirus polypeptide, a method for preparing such an avian cell, and its use in preparing an alphavirus replican particle.

Described herein, are microneedle devices comprising a recombinant alphavirus replicon encoding an exogenous polypeptide, wherein the recombinant alphavirus replicon is coated onto or embedded into a plurality of microneedles. Also described herein are methods of preparing a microneedle device comprising a recombinant alphavirus replicon encoding an exogenous polypeptide. Also disclosed herein are methods of inducing an immune response in an individual comprising contacting the individual with a microneedle device comprising a recombinant alphavirus replicon encoding an exogenous polypeptide.

The inventive subject matter relates to an immunogenic composition and method of enhancing immunogenicity and protective immunity induced by any subunit or whole organism vaccine or combination of vaccines comprising administering to the subject a priming immunization preparation containing an antigen or fragment thereof, said preparation being selected from the group consisting of: a recombinant virus expression system; a recombinant protein antigen or a recombinant polypeptide; a synthetic peptide; a polynucleotide vector; a whole organism or extract and combinations thereof; and a boosting immunization of at least one alphavirus replicon containing an antigen or fragment thereof. The inventive subject matter further relates to an immunogenic composition and method of inducing an immune response that activates both cellular and humoral arms of the immune system.

Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.

An alphavirus vector system comprising nucleic acid of a human papilloma virus origin is disclosed. A method of treating or preventing cervical cancer is also disclosed. The method includes administering the alphavirus vector system and/or a cell comprising nucleic acid derived from human papilloma virus (HPV) to a subject. The alphavirus vector system or the cell may be administered as a vaccine.

Disclosed are methods for preparing dried (preferably lyophilized) preparations comprising a population of alphaviruses or alphavirus replicon particles, a sugar or polyol, a surfactant and a salt and preparations made by said methods, both in the dried form but also as liquids prior to drying or after reconstituting dried preparations. These preparations may further comprise a plasticizer and/or a bulking agent. These preparations are readily reconstituted, with little or no loss in infectivity of the viruses or replicon particles.

Viral replicon selected nucleic acid expression libraries are useful for analyzing multiple antigens associated with a parasite, pathogen or neoplasia or for preparing immunogenic compositions for generating immune responses specific for the parasite, pathogen or neoplasia. Alphavirus replicon particles representative of the nucleic acid expression library are preferred. The nucleic acid library can be a random library, or it can be prepared after a selection step, for example, by differential hybridization prior to cloning into the replicon vector.