Arizona State University

Boyce Thompson Institute for Plant Research

Other

Dow Agrosciences LLC

Health Research, Inc.

The Texas A&m University System

Arizona Board of Regents, a Body Corporate

Hugh S Mason

Charles Joel Arntzen

Andrew Diamos

Mary Pardhe

Yasmin M Thanavala

Kenneth Roland

Dwayne D Kirk

Sun Hee Rosenthal

Brandon Favre

Guy A Cardineau

Qiang Chen

Brooke Hjelm

Joyce M VanEck

Amanda Maree Walmsley

Zhong Huang

Shuo Yuan

Timothy David Jones

Hermona Soreq

John D Clements

Koen Hellendoorn

Tsafrir Mor

Kenneth E Palmer

Xiuren Zhang

William Do Hamilton

Sean Winkle

Elizabeth Richter

Haq A Tariq

Seong Hee Bhoo

Kathleen L Hefferon

Tsafrir S Mor

Tariq A Haq

Dwayne Kirk

Amanda Walmsley

Improved plant transient expression systems using optimized geminiviral vectors that efficiently produce heteromultimeric proteins are described herein. Examples of high yields are shown herein, including two, three, or four fluorescent proteins coexpressed simultaneously. Various antibodies were produced using the optimized vectors with special focus given to the creation and production of a chimeric broadly neutralizing anti-flavivirus antibody. The variable regions of this murine antibody, 2A10G6, were codon optimized and fused to a human IgG1. Analysis of the chimeric antibody showed that it was efficiently expressed in plants, can be purified to near homogeneity by a simple one-step purification process, retains its ability to recognize the Zika virus envelope protein, and induce an immune response against Zika virus. Two other monoclonal antibodies were produced at similar levels. This technology is versatile tool for the production of a wide spectrum of pharmaceutical multi-protein complexes in a fast, powerful, and cost-effective way.

Optimized plant expression systems

The present disclosure relates to plant-based recombinant protein production systems and their methods of production and use. The plant-based recombinant protein production system is a vector comprising a 5' UTR and a 3′ UTR, wherein the 3′ UTR comprises at least one terminator selected from the group consisting of: EU, IEU, NbACT3, NbACT617, NbACT567, Pin2, BDB501, BDB282, NbHSP, NbHSPb, Rep, RbcS, SIR, SIR 5′/3′, SIR 3′, AtHSP, 35S, RepA, NOS, TMV, TNVD, PEMV, and BYDV. In certain implementations, the vector comprises two terminators in the 3′ UTR, where the two terminators are fused to form a double terminator. For example, the double terminator comprises two members selected from the group consisting of: EU, IEU, NbACT3, NbACT617, NbACT567, Pin2, BDB501, BDB282, NbHSP, NbHSPb, Rep, RbcS, SIR, SIR 5′/3′, SIR 3′, AtHSP, 35S, RepA, NOS, TMV, TNVD, PEMV, and BYDV. In some aspects, the vector further comprises a chromatin scaffold/matrix attachment region (MAR) that is downstream of the terminators.

Replicating and non-replicating vectors for recombinant protein production in plants and method of use thereof

The disclosure relates to vaccination compositions, for example, against human papillomavirus, Zika virus, and flu virus. The disclosure also relates to vectors for producing the virus-like particles and immune complex platforms of the vaccination compositions.

Universal vaccine platform

In certain embodiments, the present invention provides a poultry vaccine comprising an antigenic protein comprising a PlcC protein unit that is operably linked to a peptide linker that is operably linked to a NetB protein unit, where the vaccine is effective in stimulating a protective cellular and/or humoral immune response to. Methods are also provided for making the vaccine and for vaccinating poultry by administering such a vaccine.

Vaccine for prevention of necrotic enteritis in poultry

A single vector or multiple separate vectors that contain two or more non-competing replicons for transient expression of the heavy and light chains of Rituximab inleaves is described. The correct assembly of these subunit proteins into functional oligomeric structures to optimize the expression is also described. This system advances plant transient expression technology by eliminating the need for non-competing viruses, and thus, enhances the realistic commercial application of the multi-replicon single vector system for producing Rituximab in plant cells.

Geminiviral vector for expression of rituximab

Disclosed herein are compositions and methods for eliciting immune responses against HCV antigens. In particular embodiments, the compounds and methods elicit immune responses against all or a segment of HCV glycoprotein E1 and/or HCV glycoprotein E2.

Methods and compositions related to glycoprotein-immunoglobulin fusions

Plant viral vectors have great potential in rapid production of proteins, but no simple Here a geminivirus-based system for high-yield and rapid production of oligomeric protein complexes, including virus-like particle (VLP) vaccines and monoclonal antibodies (mAbs) is described. In particular, a single vector that contains two non-competing replicons for transient expression inleaves is described. The correct assembly of these subunit proteins into functional oligomeric structures (VLPs or full-size mAb) is also described. This system advances plant transient expression technology by eliminating the need for non-competing viruses, and thus, enhances the realistic commercial application of this technology for producing multiple-subunit protein complexes.

DNA replicon system for high-level rapid production of vaccines and monoclonal antibody therapeutics in plants

Plant viral vectors have great potential in rapid production of proteins, but no simple. Here a geminivirus-based system for high-yield and rapid production of oligomeric protein complexes, including virus-like particle (VLP) vaccines and monoclonal antibodies (mAbs) is described. In particular, a single vector that contains two non-competing replicons for transient expression inleaves is described. The correct assembly of these subunit proteins into functional oligomeric structures (VLPs or full-size mAb) is also described. This system advances plant transient expression technology by eliminating the need for non-competing viruses, and thus, enhances the realistic commercial application of this technology for producing multiple-subunit protein complexes.

The present invention relates to a synthetic plant-optimized nucleic acid molecule having a Norwalk virus capsid protein coding nucleotide sequence, and nucleic acid constructs, host cells, expression systems, and plants having the plant-optimized Norwalk virus nucleic acid molecule. The present invention also relates to a method of producing Norwalk virus capsid protein virus-like particles in a transgenic plant or transgenic plant seed transformed with a plant-optimized nucleic acid molecule encoding Norwalk virus capsid protein. The plant or a component thereof can be administered to a subject under conditions effective to immunize the subject against disease resulting from infection by a, including Norwalk virus. An oral vaccine for immunization of a subject against Norwalk virus infection is also disclosed.

Vectors and methods for immunization against norovirus using transgenic plants

A method for obtaining an immune response to a non-enteric pathogen antigen (NEPA) such as hepatitis B surface antigen (HBsAg) by feeding the antigen in a plant material to an animal that is immunoreceptive to the NEPA. It has now been discovered that the animal may be made immunoreceptive to the NEPA such as HBsAg by administering the plant material containing the NEPA in conjunction with a suitable adjuvant. The plant material is a substance comprising a physiologically acceptable plant material, especially potatoes, containing the NEPA, e.g. hepatitis B surface antigen (HBsAg). The NEPA, e.g. HBsAg in the plant results from expression by the plant of the NEPA due to genetic alteration.

Oral immunology using plant product containing a non-enteric pathogen antigen

A method for obtaining an immune response to hepatitis B surface antigen (HBsAg) by feeding the antigen in a plant material to an animal that is immunoreceptive to the HBsAg. It has now been discovered that the animal may be made immunoreceptive to HBsAg either by administering the plant material containing HBsAg in conjunction with a suitable adjuvant or by prior primary immunization. When the animal is made immunoreceptive by a prior, e.g. primary, immunization, an immune response to HBsAg may be boosted in the animal by feeding the animal the plant material containing the HBsAg. For example, an animal, e.g. a human, that previously had a positive response to primary immunization against hepatitis B, can have a booster response to HBsAg by feeding the animal the antigen in a plant material. The plant material is a substance comprising a physiologically acceptable plant material, especially potatoes, containing hepatitis B surface antigen (HBsAg). The HBsAg in the plant results from expression by the plant of HBsAg due to genetic alteration.

Oral immunology using plant product containing hepatitis surface antigen

Growing community of inventors

Ithaca, NY, United States of America

Hugh S Mason