Alphavax, Incorporated

US Government As Represented by the Secretary of the Army

The University of North Carolina at Chapel Hill

United States of America As Represented by the Secretary of the Air Force

Other

North Carolina State University

Aphavax, Inc.

Jonathan F Smith

Peter M Pushko

Michael D Parker

Kurt Iver Kamrud

Robert E Johnston

Nancy L Davis

Bolyn Hubby

George Ludwig

Jon O Rayner

John S Lee

Sergey A Dryga

Alan L Schmaljohn

Elizabeth A Reap

Hengky Chandrahalim

Michael C Hevey

Ian Caley

Maureen Maughan

Laura Copp

Vernon McNeil Coffield, Iii

Robert G Ulrich

Susan L Welkos

Diane L Negley

Bruce J Crise

Franziska B Grieder

Jonathan O Rayner

Maureen F Maughan

Bryan A Coppes

Leonard A Smith

Mary Kate Hart

Julie A Wilson

Mark T Dertzbaugh

Whitney Ellis

Shannon M Schmura

Mark Steven Oberste

Loretta V Willis

Diane I Negley

Harold Alterson

Kim Butler

Peter Berglund

Ian J Caley

Kim Alterson

Vernon Mcneil Coffield Iii

A passive microscopic Fabry-P&#xe9;rot Interferometer (FPI) sensor includes an optical fiber a three-dimensional microscopic optical structure formed on a cleaved tip of an optical fighter that reflects a light signal back through the optical fiber. The reflected light is altered by refractive index changes in the three-dimensional structure that is subject to at least one of: (i) thermal radiation; and (ii) volatile organic compounds.

Temperature-immune self-referencing Fabry-P&#xe9;rot cavity sensors

A method of making passive microscopic Fabry-P&#xe9;rot Interferometer (FPI) sensor includes forming a three-dimensional microscopic optical structure on a cleaved tip of an optical fiber that reflects a light signal back through the optical fiber. The reflected light is altered by refractive index changes in the three-dimensional structure that is subject to at least one of: (i) thermal radiation; and (ii) volatile organic compounds.

Method of making temperature-immune self-referencing Fabry-P&#xe9;rot cavity sensors

A passive microscopic Fabry-P&#xe9;rot Interferometer (FPI) sensor an optical fiber a three-dimensional microscopic optical structure formed on a cleaved tip of an optical fighter that reflects a light signal back through the optical fiber. The reflected light is altered by refractive index changes in the three-dimensional structure that is subject to at least one of: (i) thermal radiation; and (ii) volatile organic compounds.

The present disclosure provides TC-83 VEE-derived replicons, alphaviral replicon particles and immunogenic compositions containing TC-83 alphaviral replicon particles which direct the expression of at least one antigen when introduced into a suitable host cell. The TC-83 VEE-derived ARPs described herein are improved in that they are subject to a lower vector-specific immune response than prior art ARPs.

TC-83-derived alphavirus vectors, particles and methods

Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector of replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Use of microRNAs to control virus helper nucleic acids

The immune response to an antigen of interest, especially one in purified form, can be significantly enhanced by the simultaneous administration of an alphavirus replicon particle which expresses the same antigen. This allows for the use of significantly smaller quantities of the protein antigen than in conventional immunization strategies, and this new immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Alphavirus replicon particles matched to protein antigens as immunological adjuvants

Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

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.

Multi-antigenic alphavirus replicon particles and methods

The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5' replication recognition sequence, wherein at least one initiation codon has been removed from the 5&#x2032; replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3&#x2032; replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5&#x2032; and 3&#x2032; replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus non-structural proteins.

Promoterless cassettes for expression of alpha virus structural proteins

The immune response to an antigen of interest, either in purified form or expressed via an alphavirus replicon particle, can be enhanced by the simultaneous administration of an alphavirus replicon particle which expresses interleukin-12. This allows for the use of significantly smaller quantities of the antigen and this immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

Alphavirus replicon particles as immunological adjuvants

Growing community of inventors

Cary, NC, United States of America

Jonathan F Smith