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Dive into the research topics where Barry Bratcher is active.

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Featured researches published by Barry Bratcher.


Proceedings of the National Academy of Sciences of the United States of America | 2012

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

Gene G. Olinger; James Pettitt; Do Han Kim; Ognian Bohorov; Barry Bratcher; Ernie Hiatt; Steven D. Hume; Ashley K. Johnson; Josh Morton; Michael Pauly; Kevin J. Whaley; Calli Lear; Julia E. Biggins; Corinne Scully; Lisa E. Hensley; Larry Zeitlin

Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.


Proceedings of the National Academy of Sciences of the United States of America | 2009

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component

Barry R. O'Keefe; Fakhrieh S. Vojdani; Viviana Buffa; Robin J. Shattock; David C. Montefiori; James Bakke; Jon C. Mirsalis; Annalisa D'Andrea; Steven D. Hume; Barry Bratcher; Carrie J. Saucedo; James B. McMahon; Gregory P. Pogue; Kenneth E. Palmer

To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing GRFT. Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, we also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes.


Science Translational Medicine | 2013

Therapeutic Intervention of Ebola Virus Infection in Rhesus Macaques with the MB-003 Monoclonal Antibody Cocktail

James Pettitt; Larry Zeitlin; Do Han Kim; Joshua C. Johnson; Ognian Bohorov; Barry Bratcher; Ernie Hiatt; Steven D. Hume; Ashley K. Johnson; Josh Morton; Michael Pauly; Kevin J. Whaley; Michael F. Ingram; Ashley Zovanyi; Megan L. Heinrich; Ashley Piper; Justine M. Zelko; Gene G. Olinger

Ebola virus–infected macaques were successfully treated with a cocktail of monoclonals manufactured in plants. Better Late than Never They say prevention is better than a cure, but sometimes, immediate action isn’t possible. This is especially the case for a deadly disease such as Ebola virus (EBOV) infection, where sporadic outbreaks make it hard to predict when and where treatment will be needed. In patients, neither preventative nor therapeutic options are currently available, but recent studies have shown that a cocktail of monoclonal antibodies may help if given within 1 to 2 days of challenge in macaques. Pettitt et al. now extend this window, showing that this antibody cocktail can be used as a therapeutic in nonhuman primates (NHPs) even after the onset of symptoms. The authors challenged NHPs with EBOV and didn’t begin treatment until after confirmation of infection and observation of fever. Although the controls here and all historical controls succumbed to infection, 43% of the treated animals survived the challenge. If these observations hold true in humans, these monoclonal antibodies could give hope to people exposed to EBOV. Ebola virus (EBOV) remains one of the most lethal transmissible infections and is responsible for high fatality rates and substantial morbidity during sporadic outbreaks. With increasing human incursions into endemic regions and the reported possibility of airborne transmission, EBOV is a high-priority public health threat for which no preventive or therapeutic options are currently available. Recent studies have demonstrated that cocktails of monoclonal antibodies are effective at preventing morbidity and mortality in nonhuman primates (NHPs) when administered as a post-exposure prophylactic within 1 or 2 days of challenge. To test whether one of these cocktails (MB-003) demonstrates efficacy as a therapeutic (after the onset of symptoms), we challenged NHPs with EBOV and initiated treatment upon confirmation of infection according to a diagnostic protocol for U.S. Food and Drug Administration Emergency Use Authorization and observation of a documented fever. Of the treated animals, 43% survived challenge, whereas both the controls and all historical controls with the same challenge stock succumbed to infection. These results represent successful therapy of EBOV infection in NHPs.


Human Vaccines & Immunotherapeutics | 2014

Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

Jyothi K. Mallajosyula; Ernie Hiatt; Steve Hume; Ashley K. Johnson; Trushar Jeevan; Rachel Chikwamba; Gregory P. Pogue; Barry Bratcher; Hugh Haydon; Richard J. Webby; Alison A. McCormick

Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.


Current Topics in Microbiology and Immunology | 2012

Emerging antibody-based products.

Kevin J. Whaley; Josh Morton; Steve Hume; Ernie Hiatt; Barry Bratcher; Victor Klimyuk; Andrew Hiatt; Michael Pauly; Larry Zeitlin

Antibody-based products are not widely available to address many global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. There are now tremendous opportunities to address these industrialization challenges as a result of revolutionary advances in plant virus-based transient expression. This review focuses on some antibody-based products that are in preclinical and clinical development, and have scaled up manufacturing and purification (mg of purified mAb/kg of biomass). Plant virus-based antibody products provide lower upfront cost, shorter time to clinical and market supply, and lower cost of goods (COGs). Further, some plant virus-based mAbs may provide improvements in pharmacokinetics, safety and efficacy.


Archive | 2014

Production of Pharmaceutical Grade Recombinant Native Aprotinin and Non-oxidized Aprotinin Variants Under Greenhouse and Field Conditions

Gregory P. Pogue; Fakhrieh S. Vojdani; Kenneth E. Palmer; Earl L. White; Hugh Haydon; Barry Bratcher

Recombinant bovine pancreatic aprotinin was produced in Nicotiana species (N. benthamiana and N. excelsiana), a transient expression vector derived from the tobacco mosaic virus genome. Animal-source-free recombinant aprotinin was made in plants grown under controlled (greenhouse) conditions and in the field. Product purified from both production environments showed virtually identical performance and specifications as the bovine-derived pharmaceutical product. Further, the product has excellent stability characteristics and is currently being marketed as a cell culture excipient. Issues, such as oxidative variation of aprotinin product, were addressed by changing growth conditions and by substitution of amino acids for the site of oxidation. The resulting aprotinin variants showed no oxidation, yet retained full activity and production yields. The production parameters of aprotinin provide an affordable way to make high-quality pharmaceuticals in plants. The speed and flexibility of transient expression also allows rapid tailoring of products to address biochemical challenges and product requirements.


Plant Biotechnology Journal | 2010

Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems.

Gregory P. Pogue; Fakhrieh S. Vojdani; Kenneth E. Palmer; Ernie Hiatt; Steve Hume; Jim Phelps; Lori Long; Natasha Bohorova; Do Han Kim; Michael Pauly; Jesus Velasco; Kevin J. Whaley; Larry Zeitlin; Stephen J. Garger; Earl L. White; Yun Bai; Hugh Haydon; Barry Bratcher


Archive | 2004

Flexible processing apparatus for isolating and purifying viruses, soluble proteins and peptides from plant sources

Barry Bratcher; Stephen J. Garger; R. Barry Holtz; Michael J. McCulloch


Archive | 2011

SMOKELESS TOBACCO PASTILLE AND MOULDING PROCESS FOR FORMING SMOKELESS TOBACCO PRODUCTS

Daniel Verdin Cantrell; Joshua D. Morton; Steven D. Hume; Barry Bratcher; Robert Frank Boutin; Thomas Hinkemeyer; Thaddeus J. Jackson


Archive | 2011

Tobacco separation process for extracting tobacco-derived materials, and associated extraction systems

Joshua D. Morton; Steven D. Hume; Barry Bratcher

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Steven D. Hume

University of Arkansas for Medical Sciences

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Joshua D. Morton

R. J. Reynolds Tobacco Company

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Larry Zeitlin

Johns Hopkins University

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Gregory P. Pogue

University of Texas at Austin

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Kyle Ford

R. J. Reynolds Tobacco Company

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Leigh Ann Blevins Joyce

R. J. Reynolds Tobacco Company

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Leigh Hagan

R. J. Reynolds Tobacco Company

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