University of Texas System

Other

The Uab Research Foundation

Novartis Vaccines & Diagnostics, Gmbh

Novartis Ag

Washington University

Ilya V Frolov

Elena Frolova

Thomas W Dubensky, Jr

John M Polo

Sondra Schlesinger

Scott C Weaver

Barbara A Belli

Sergey A Dryga

Peter W Mason

Susan Barnett

Gillis Otten

David A Driver

Jason P Gardner

Alexandr V Shustov

Eryu Wang

Sergey A Drvga

Peter C Mason

The present invention discloses an attenuated recombinant alphavirus that is incapable of replicating in mosquito cells and of transmission by mosquito vectors. These attenuated alphavirus may include but is not limited to Western Equine Encephalitis virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus or Chikungunya virus. The present invention also discloses the method of generating such alphaviruses and their use as immunogenic compositions.

Attenuated recombinant alphaviruses incapable of replicating in mosquitoes and uses thereof

The present invention provides pseudoinfectious alphavirus particles and methods of making them and using them to produce an immune response to an alphavirus in a subject.

Methods and compositions for pseudoinfectious alphaviruses

The present invention discloses a replication-deficient pseudoinfective virus belonging to the Flaviviridae family that lack the capsid gene, where the replication-deficient pseudoinfective virus propagates only in cells expressing the capsid or capsid, prM and envelope protein of the flavivirus. The present also discloses the method of producing such viruses on a large scale and the use of these pseudoinfective viruses as vaccines for preventing diseases caused by infections of humans or animals by the viruses belonging to this family.

Pseudoinfectious flavivirus and uses thereof

The present invention provides alphavirus replicons and methods of their use in producing heterologous protein.

Methods and compositions for alphavirus replicons

The present invention discloses a chimeric alphavirus comprising a Sindbis virus cDNA fragment, an Eastern equine encephalitis virus cDNA fragment, a Western equine encephalitis virus cDNA fragment or a combination thereof. The present also discloses the use of this chimeric alphavirus as vaccines and in serological and diagnostic assays.

Chimeric sindbis-western equine encephalitis virus and uses thereof

Compositions and methods are provided for Eukaryotic Layered Vector Initiation Systems andreplicon particles for introducing heterologous sequences into cells for generating immune responses.

Compositions and methods for generating an immune response utilizing alphavirus-based vector systems

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, &#x2dc;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, C30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of C, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of Cby 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.

Attenuation of encephalitogenic alphavirus and uses thereof

The present invention discloses a two-component genome flavivirus and a method for propagating such virus. Since the genetic material of this flavivirus is distributed between two genomes, the flavivirus is deficient in replication, incapable of causing disease but capable of inducing an immune response. Nevertheless, the design of the replication deficient flavivirus discussed herein allows propagation of these flaviviruses at industrial level.

Two-component genome flavivirus and uses thereof

The present invention discloses a chimeric Chikungunya virus comprising a heterologous alphavirus cDNA fragment and a Chikungunya virus cDNA fragment. The heterologous alphavirus may include but is not limited to Sindbis virus, Eastern equine encephalitis virus or Venezuelan equine encephalitis virus. The present invention also discloses the use of this chimeric Chikungunya virus as vaccines and in serological and diagnostic assays.

Chimeric chikungunya virus and uses thereof

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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.

Recombinant alphavirus-based vectors with reduced inhibition of cellular macromolecular synthesis

Methods are provided for generating immune responses utilizing alphavirus-based vector systems.

The present invention provides a Venezuelan equine encephalitis virus replicon RNA useful in the development of stable lines of mammalian, avian and insect cells in which these replicons will persistently replicate. Venezuelan equine encephalitis (VEE) virus replicons contain a number of unique adaptive mutations that make the replicons noncytopathic. The replicons remain resistant to IFN-&#x3b1;/&#x3b2;. Replicon replication leads to high-level production of heterologous proteins, which are encoded by the replicons' genome and are under the control of a viral subgenomic promoter. Also provided are methods of screening for inhibitory compounds of Venezuelan equine encephalitis virus replication and eastern equine encephalitis virus replication.

Growing community of inventors

Birmingham, AL, United States of America

Ilya V Frolov