Novartis Vaccines & Diagnostics, Gmbh

Chiron Corporation

Other

Novartis Ag

Chiron Viagene, Inc.

Glaxosmithkline Biologicals Sa

John M Polo

Michael Houghton

Thomas W Dubensky, Jr

David A Driver

Barbara A Belli

Silvia Perri

Douglas J Jolly

Ilya V Frolov

Sondra Schlesinger

Sergey A Dryga

David Y Chien

Kent B Thudium

Susan Barnett

Gillis Otten

Jang Hyun Han

Amy J Weiner

John J Donnelly

Michael Vajdy

Carlos E Ibanez

Stephen F Hardy

Catherine Greer

Stephen M W Chang

Stephen M Chang

Zequn Tang

Jason P Gardner

Timothy C Fong

Sergey A Drvga

Ilva Frolov

Yasushi Uematsu

Barbara Beli

Steven Mw Chang

Nicholas Valiante

Vega Masignani

Sylvia Perri

Konrad Stadler

Mi Young Seo

Jens-Peter Gregersen

Rino Rappuoli

Hyun Chul Song

Hans Dieter Klenk

Thomas Dubensky

Perri Silvia

Derek O'hagan

Described herein are compositions and methods for stimulating an immune response to one or more proteins derived from one or more respiratory pathogens. In particular, the invention relates to alphavirus replicons, alphavirus vector constructs, alphavirus replicon particles expressing one or more antigens derived from one or more respiratory pathogens as well as to method of making and using these immunogenic compositions.

Alphavirus vectors for respiratory pathogen vaccines

Chimeric alphavirus particles and alphavirus replicon RNAs are provided including methods of making and using same. The alphavirus replicon RNAs comprise deletions in one or more nonstructural proteins. Methods of making, using, and therapeutic preparations containing the chimeric alphavirus particle are disclosed.

Chimeric alphavirus replicon particles

Provided herein are modified, functional 5' amplification sequences that are defective packaging signals. Also provided are compositions and methods comprising these modified 5&#x2032; amplification sequences.

Alphavirus replicon packaging constructs

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

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.

The present disclosure provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems.

Eukaryotic layered vector initiation systems

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.

Expression cassettes are provided comprising a promoter operably linked to a nucleic acid molecule which, when transcribed in vivo, forms double-stranded RNA that induces the production of interferon. Expression cassettes also are provided comprising a promoter operably linked to a ribozyme or antisense nucleic acid molecule which, when transcribed in vivo, forms a ribozyme or antisense RNA molecule that stimulates an immune response. In addition, expression cassettes are provided comprising a promoter operably linked to a ribozyme or antisense nucleic acid molecule which, when transcribed in vivo, stimulates apoptosis. Finally, gene delivery vectors are provided which contain such expression cassettes, host cells containing the gene delivery vectors, and methods of utilizing the expression cassettes, gene delivery vectors, and host cells.

Enhancement of the immune response for vaccine and gene therapy applications

Chimeric alphaviruses andreplicon particles are provided including methods of making and using same. Specifically,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 chimericparticle, are disclosed.

The present invention provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems.

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.

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.

Method for the quantitation of alphavirus replicon particles

Growing community of inventors

Encinitas, CA, United States of America

John M Polo