United States of America, As Represented by the Secretary of Agriculture

Lawrence Livermore National Security, LLC

University of Connecticut

Codagenix, Inc.

Teresa B De Los Santos

Fayna C Diaz-San Segundo

Aida Elizabeth Rieder

Paul D Hoeprich

Luis Leandro Rodriguez

Marvin J Grubman

Marla J Koster

James J Zhu

Devendra Rai

Steffen Mueller

John Robert Coleman

Anna Kloc

Gisselle N Medina

Genetically engineered Foot and Mouth Disease Virus (FMDV) and related engineered proteins and polynucleotides, nanolipoprotein particles, compositions, methods and systems are described. The genetically engineered FMDV is modified by the strategic insertion of a protein tag into select regions of the FMDV genome which encode viral proteins that are exposed on the surface of the FMDV viral capsid. The inserted protein tag is displayed as a decoration or attachment on the viral capsid surface.

Genetically engineered foot and mouth disease virus and related proteins, polynucleotides, compositions, methods and systems

The present disclosure describes deoptimized foot and mouth viruses and their use for prophylactic and therapeutic treatment of mammalian subjects. The recombinant viruses provided herein include alterations in several genomic regions as well as Differentiating Infected from Vaccinated Animals (DIVA) markers.

Live attenuated strains of foot and mouth disease modified by deoptimization and uses thereof

Genetically engineered Foot and Mouth Disease Virus and related proteins, polynucleotides, compositions, methods and systems

A member of the bovine type III IFN family, boIFN-&#x3bb;3, was identified and characterized. We expressed boIFN-&#x3bb;3 using a recombinant replication defective human adenovirus type 5 (Ad5) and demonstrated antiviral activity against foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) in bovine cells in vitro. Cattle were inoculated with Ad5-boIFN-&#x3bb;3 followed by intradermolingual or aerosol FMDV challenge. Results demonstrated that the type III IFN family is conserved in bovines and that treatment of cattle with boIFN-&#x3bb;3 alone or in combination with IFN-&#x3b1; is able to confer delayed and reduced severity of FMD. Furthermore inoculation with Ad5-boIFN-&#x3bb;3 alone conferred full protection against aerosol challenge for at least 7 days after administration suggesting that type III IFN used in combination with FMD vaccines could fill one of the current gaps in emergency vaccination against FMDV.

Antiviral activity of bovine type III interferon against foot-and-mouth disease virus

Previously we have identified a conserved domain (SAP, for SAF-A/B, Acinus, and PIAS) in the foot-and-mouth disease virus (FMDV) leader (L) protein coding region that is required for proper sub-cellular localization and function. Mutation of isoleucine 55 and leucine 58 to alanine (I55A, L58A) within the SAP domain resulted in a viable virus that displayed a mild attenuated phenotype in cell culture, along with altered sub-cellular distribution of L and failure to induce degradation of the transcription factor nuclear factor kappa-B. Here we report that inoculation of swine and cattle with this mutant virus results in the absence of clinical disease, the induction of a significant FMDV-specific neutralizing antibody response, and protection against subsequent homologous virus challenge. Remarkably, swine vaccinated with SAP mutant virus are protected against wild type virus challenge as early as two days post-vaccination suggesting that a strong innate as well as adaptive immunity is elicited. This variant could serve as the basis for construction of a live-attenuated FMD vaccine candidate.

Recombinant live attenuated foot-and-mouth disease (FMD) vaccine containing mutations in the L protein coding region

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Miller Place, NY, United States of America

Teresa B De Los Santos