Soymeds, Inc.

DAVIDSON, NC, United States

Soymeds, Inc.

DAVIDSON, NC, United States

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Hudson L.C.,Soymeds, Inc. | Garg R.,Soymeds, Inc. | Garg R.,Chandigarh Institute of Microbial Technology | Bost K.L.,Soymeds, Inc. | And 3 more authors.
BioMed Research International | Year: 2014

Soybean seeds possess several inherent qualities that make them an ideal host for the production of biopharmaceuticals when compared with other plant-based and non-plant-based recombinant expression systems (e.g., low cost of production, high protein to biomass ratio, long-term stability of seed proteins under ambient conditions, etc.). To demonstrate the practicality and feasibility of this platform for the production of subunit vaccines, we chose to express and characterize a nontoxic form of S. aureus enterotoxin B (mSEB) as a model vaccine candidate. We show that soy-mSEB was produced at a high vaccine to biomass ratio and represented 76 theoretical doses of human vaccine per single soybean seed. We localized the model vaccine candidate both intracellularly and extracellularly and found no difference in mSEB protein stability or accumulation relative to subcellular environment. We also show that the model vaccine was biochemically and immunologically similar to native and recombinant forms of the protein produced in a bacterial expression system. Immunization of mice with seed extracts containing mSEB mounted a significant immune response within 14 days of the first injection. Taken together, our results highlight the practicality of soybean seeds as a potential platform for the production of functional subunit vaccines. © 2014 Laura C. Hudson et al.


Hudson L.C.,University of North Carolina at Charlotte | Hudson L.C.,Soymeds, Inc. | Seabolt B.S.,North Carolina State University | Odle J.,North Carolina State University | And 5 more authors.
Clinical and Vaccine Immunology | Year: 2013

In an effort to develop a sustainable platform for manufacturing protein-based vaccine candidates, we expressed a triple mutant of staphylococcal enterotoxin B carrying the L45R, Y89A, and Y94A modifications in transgenic soybean seeds (soy-mSEB). SoymSEB possessed no detectable superantigen activity in vitro. We found that this soybean-derived, nontoxic mutant of SEB could be stably expressed, stored in seeds for extended periods at room temperature without degradation, and easily purified from contaminating soy proteins. Vaccination of pigs with purified soy-mSEB, or the identical triple mutant expressed in Escherichia coli (E. coli-mSEB), resulted in high antibody titers against the native toxin in immunized animals. In fact, titers were indistinguishable regardless of the immunogen used, demonstrating the equivalence of soy-mSEB and E. coli-mSEB vaccinations. Antisera from either immunized group were able to block native SEB superantigen activity in an in vitro neutralization assay. Similar results were obtained when immunized animals were challenged with a sublethal dose of native toxin. Significant reductions in toxin-induced serum cytokine levels were observed in soy-mSEB- and E. coli-mSEB-immunized pigs compared to control animals. The reductions in SEB-induced cytokine responses were similar regardless of the immunogen used for vaccination. Surprisingly, however, some clinical symptoms, such as prostration, lethargy, emesis, and/or diarrhea, were still observed in all immunized animals. These studies demonstrate the potential for soybean-derived proteins as a platform technology for sustainable vaccine manufacturing and the usefulness of a sublethal challenge model in pigs for evaluating the efficacy of potential SEB vaccine candidates. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Powell R.,University of North Carolina at Charlotte | Hudson L.C.,Soymeds, Inc. | Lambirth K.C.,Soymeds, Inc. | Luth D.,Iowa State University | And 5 more authors.
Plant Cell Reports | Year: 2011

Soybean seeds possess many qualities that make them ideal targets for the production of recombinant proteins. However, one quality often overlooked is their ability to stockpile large amounts of complex storage proteins. Because of this characteristic, we hypothesized that soybean seeds would support recombinant expression of large and complex proteins that are currently difficult or impossible to express using traditional plant and non-plant-based host systems. To test this hypothesis, we transformed soybeans with a synthetic gene encoding human thyroglobulin (hTG)-a 660 kDa homodimeric protein that is widely used in the diagnostic industry for screening and detection of thyroid disease. In the absence of a recombinant system that can produce recombinant hTG, research and diagnostic grade hTG continues to be purified from cadaver and surgically removed thyroid tissue. These less-than-ideal tissue sources lack uniform glycosylation and iodination and therefore introduce variability when purified hTG is used in sensitive ELISA screens. In this study, we report the successful expression of recombinant hTG in soybean seeds. Authenticity of the soy-derived protein was demonstrated using commercial ELISA kits developed specifically for the detection of hTG in patient sera. Western analyses and gel filtration chromatography demonstrated that recombinant hTG and thyroid-purified hTG are biologically similar with respect to size, mass, charge and subunit interaction. The recombinant protein was stable over three generations and accumulated to ~1. 5% of total soluble seed protein. These results support our hypothesis that soybeans represent a practical alternative to traditional host systems for the expression of large and complex proteins. © 2011 Springer-Verlag.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.18M | Year: 2013

DESCRIPTION provided by applicant Thyroid cancer is the most common type of endocrine malignancy New thyroid cancers patients are identified daily and most patients live for decades following diagnosis Thyroglobulin TG levels in the sera or in fine needle biopsies of thyroid cancer patients are routinely quantified using various agency approved e g FDA immunoassays for diagnostic and prognostic purposes In fact immunoassays to quantify TG levels are the gold standard for the diagnosis and monitoring process for these patients One would anticipate that such frequently prescribed immunoassays would be highly reliable and easily interpreted Unfortunately this is not the case The limitations of present day TG IVD immunoassays begin with the analytes required for their construction Presently TG must be obtained from human cadavers or from discarded human surgical tissue This creates significant costs when purifying the protein from gland homogenates and the problem of lot to lot variation by supplier can be considerable Furthermore the presence of autoantibodies against TG in the sera of patients can interfere with these assays and their interpretation Presently there is no solution to these problems or limitations In this Phase II SBIR we will continue our efforts to provide new solutions for both these problems Using a novel platform technology we have successfully expressed full length human TG in transgenic soybean seeds To our knowledge this is the only source of recombinant human TG and is the only successful expression of this protein using any protein expression system We propose that this renewable source of TG will prove to be more homogenous easier to produce and easier to purify than thyroid derived TG Further we propose the construction of a device that can be used for the elimination of anti TG autoantibodies from the sera of patients that can interfere with these immunoassays If successful these accomplishments should significantly enhance present day TG immunoassays designed to diagnose and monitor patients with thyroid cancers PUBLIC HEALTH RELEVANCE In this Phase II SBIR we will continue our efforts to solve two of the most significant problems plaguing FDA approved thyroglobulin TG immunoassays Expressing full length human TG in transgenic soybean seeds provides a renewable source of this analyte which has properties superior to the variability seen with lots of protein purified frm thyroid tissues Furthermore the unique advantages of transgenic soybean derived proteins will allow for the first time a practical solution for the elimination of anti TG autoantibodies that an interfere with immunoassays These accomplishments should significantly enhance present day TG immunoassays designed to diagnose and monitor patients with thyroid cancers


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 216.22K | Year: 2010

DESCRIPTION (provided by applicant): Thyroglobulin levels in the sera of thyroid cancer patients are routinely quantified using various agency-approved (e.g. FDA) immunoassays. Physicians frequently order these diagnostic immunoassays to determine thyroglobulin levels in their patients. Therefore it is not surprising that many different companies have developed their own diagnostic tests for purchase and use in the clinical laboratory. Despite the current availability of these numerous thyroglobulin immunoassays, each suffers from inherent limitations. In fact, it is not possible to accurately compare the results obtained from one thyroglobulin immunoassay with those obtained by another. There are two major problems which need to be solved. First, the lack of a universally consistent thyroglobulin standard contributes significantly to variability between FDA-approved immunoassays made by different suppliers. Presently, the only source of human thyroglobulin for use as a standard in immunoassays comes from cadavers or surgically removed human thyroid tissue. The heterogeneity of different lots of human-derived thyroglobulin is a limitation which has not been solved. Second, anti-thyroglobulin autoantibodies present in some thyroid cancer patients' sera can interfere with immunoassays that attempt to detect and quantify thyroglobulin. Currently, there are no clear solutions to either of these dilemmas. In this Phase I SBIR, we propose to solve two of the most significant problems plaguing FDA-approved thyroglobulin immunoassays by expressing human thyroglobulin in transgenic soybean seeds for use as a class II medical device analyte. Taking advantage of this novel platform for expressing thyroglobulin should allow us to produce a highly homogenous standard for immunoassays. Furthermore, the unique advantages of transgenic soybean-derived proteins (e.g. homogeneity, ease of purification, very low cost, elimination of human pathogen transmission, renewable green technology , etc.) will allow, for the first time, a practical solution for the elimination of anti-thyroglobulin autoantibodies that can interfere with immunoassays. These accomplishments should significantly enhance present day thyroglobulin immunoassays designed to diagnose and monitor patients with thyroid cancers. PUBLIC HEALTH RELEVANCE: In this Phase I SBIR, we propose to solve two of the most significant problems plaguing FDA-approved thyroglobulin immunoassays by expressing human thyroglobulin in transgenic soybean seeds for use as a class II medical device analyte. Taking advantage of this novel platform for expressing thyroglobulin should allow us to produce a highly homogenous standard for immunoassays. Furthermore, this will allow a practical solution for the elimination of anti-thyroglobulin autoantibodies that can interfere with immunoassays. These accomplishments should significantly enhance present day thyroglobulin immunoassays designed to diagnose and monitor patients with thyroid cancers.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 548.42K | Year: 2016

ABSTRACT The difficulties for creating an efficacious oral autoantigen therapy are basically twofold practicality and efficacy Practically most protein autoantigens will be expensive to manufacture to administer and may not remain intact following passage through the gastrointestinal tract Therapeutically even if some of the protein autoantigens survive to interact with immune cells in the Gut Associated Lymphoid Tissue GALT their ability to significantly reduce autoimmune T and B cells responses in patients has not been effectively demonstrated Developing a routine practical strategy for oral autoantigen therapy is certainly a difficult and risky proposition Demonstrating the feasibility of a technology for routine and practical oral autoantigen therapy would be unique As a proof of principle we have expressed an autoantigen the alpha subunit of the human nicotinic acetylcholine receptor as a fusion with the reovirus sigma protein in transgenic soybean seeds The logic behind such an approach lies in the ability of the reovirus sigma protein sigma to bind microfold cells covering mucosal lymphoid tissues Autoantigens fused to sigma target the immunogen to these cells and deliver the autoantigen in a tolerizing context to limit an ongoing autoimmune response Further while such autoantigens and fusion proteins are difficult to manufacture the ability to express large quantities of a sizeable protein and administer it as a consumable soymilk formulation is unique to this platform expression system The autoantigen that we will focus on for these studies is one that most patients with myasthenia gravis mount an immune response against i e the extracelluar portion of the nicotinic acetylcholine receptor alpha chain AChR In this proposal we will manufacture quantities of an AChR sigma concentrate made from transgenic soybean seeds expressing this fusion protein Studies to define manufacturing and encapsulation of this powdered material will be conducted We will also use a rat model to begin to define safety in vivo distribution and therapeutic efficacy using a model of experimental autoimmune myasthenia gravis Completion of these studies will address some of the most important regulatory hurdles for approval of oral soy based concentrates containing this novel fusion protein If successful the therapeutic efficacy studies will suggest that we have developed a candidate oral tolerance therapy for the autoimmune disease myasthenia gravis MG The practical advantages of soybean derived therapeutics combined with the efficacy of delivering an autoantigen in a tolerizing context to the gut immune system represent a novel solution for therapeutic intervention for myasthenia gravis and potentially many other autoimmune diseases Narrative Demonstrating the feasibility of a technology for routine and practical oral autoantigen therapy would be unique We have expressed a candidate oral tolerance therapy for myasthenia gravis using transgenic soybean seeds as the protein expression system The practical advantages of soybean derived therapeutics combined with the efficacy of delivering an autoantigen in a tolerizing context to the gut immune system represent a novel solution for therapeutic intervention for autoimmune diseases


Patent
Soymeds, Inc. | Date: 2010-01-25

The present invention relates to vaccines that are made in transgenic soybeans for use in humans, animals of agricultural importance, pets, and wildlife. These vaccines are used as vaccines against viral, bacterial, fungal, parasitic or prion related diseases, cancer antigens, toxins, and autologous or self proteins. The transgenic soybeans of the instant invention also can be used for inducing tolerance to allergens or tolerance to autoimmune antigens, wherein an individual shows hypersensitivity to said allergen or has developed autoimmunity to autologous or self proteins, respectively. The invention also relates to prophylactically treating individuals and/or populations prior to showing hypersensitivity to allergens. Other aspects of the invention include using the transgenic soybeans as an oral contraceptive, and the expression of protein adjuvants in transgenic soybeans.

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