Emerging Antibody-based Products

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

doi:10.1007/82_2012_240

Cited by 15 publications

(14 citation statements)

References 53 publications

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“…In addition to protective efficacy, issues related to platform technology, scalability, and speed of manufacturing will ultimately dictate which product(s) will be pursued for advanced development and are consistent with the unique needs for biodefense. In this regard, the Nicotiana benthamiana-based rapid antibody-manufacturing platform (RAMP) provides the potential for extremely fast and high-yield monoclonal antibody (MAb) production that has already proven to be applicable to biodefense (18)(19)(20)(21). The technology entails mass infiltration of mature Nicotiana plants with an Agrobacterium tumefaciens suspension carrying T-DNA encoding viral replicons and results in high MAb recovery from original DNA constructs within days (22).…”

mentioning

confidence: 99%

Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge

Sully

Whaley

Bohorova

et al. 2014

Clin. Vaccine Immunol.

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e Recent incidents in the United States and abroad have heightened concerns about the use of ricin toxin as a bioterrorism agent. In this study, we produced, using a robust plant-based platform, four chimeric toxin-neutralizing monoclonal antibodies that were then evaluated for the ability to passively protect mice from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was further evaluated in mice as a therapeutic following ricin exposure by injection and inhalation. Ricin toxin is a member of the medically important A-B family of plant and bacterial ribosome-inactivating proteins (RIPs) (1). In its mature form, ricin is a 65-kDa heterodimeric glycoprotein that is a natural constituent of the seeds of the castor plant (Ricinus communis). The 267-amino-acid A subunit (RTA) of ricin is an RNA N-glycosidase that depurinates a conserved adenosine residue within the so-called sarcin-ricin loop (SRL) of eukaryotic 28S rRNA, which is required for activation of the elongation factor EF-Tu (2, 3). RTA is linked via a single disulfide bond to ricin's B subunit (RTB), a 262-amino-acid lectin that is specific for glycoproteins and glycolipids terminating in galactose and Nacetylgalactosamine (Gal/GalNAc). In addition to its role in attachment, RTB also mediates the retrograde transport of ricin to the trans-Golgi network (TGN) and endoplasmic reticulum (ER), where RTA is ultimately delivered across the ER membrane and into the cytoplasm (4, 5). The extraordinary capacity of RTA to inactivate ribosomes (k cat , 1,500/min) makes ricin one of the most potent known RIPs (6, 7). For example, in rodents and nonhuman primates, the 50% lethal dose (LD 50 ) of ricin by injection is approximately 5 g/kg, while the LD 50 of ricin by inhalation is estimated to be as low as 3 g/kg (8). The respiratory mucosa is especially sensitive to ricin, as even trace amounts of toxin are known to elicit widespread necrosis in the airways and alveoli, peribronchovascular edema, mixed inflammatory cell infiltrates, and massive pulmonary alveolar flooding (9-15).The U.S. Departments of Defense (DOD) and Health and Human Services (HHS) have ongoing initiatives to develop antibody-based products capable of providing passive protection against systemic and mucosal ricin exposure (16,17). In addition to protective efficacy, issues related to platform technology, scalability, and speed of manufacturing will ultimately dictate which product(s) will be pursued for advanced development and are consistent with the unique needs for biodefense. In this regard, the Nicotiana benthamiana-based rapid antibody-manufacturing platform (RAMP) provides the potential for extremely fast and high-yield monoclonal antibody (MAb) production that has already proven to be applicable to biodefense (18-21). The technology entails mass infiltration of mature Nicotiana plants with an Agrobacterium tumefaciens suspension carrying T-DNA encoding viral replicons and results in high MAb recovery from original DNA constructs within days (22). The Nicotiana-based RAMP...

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mentioning

confidence: 99%

Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge

Sully

Whaley

Bohorova

et al. 2014

Clin. Vaccine Immunol.

Self Cite

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“…So that's why it is an integral part of various cultures and plays a key role in many shamanistic traditions. In pre-Columbian North America, various civilizations preferred it for smoking and for many other purposes e.g., healing ailments (especially to cure earaches, cuts and burns, snake bites) respiratory diseases, urinary ailments, nervous ailments, fever, convulsions and skin diseases [9,[17][18][19][20][21][22][23]. Brief description of tobacco usage history in medicine is presented in Table 2.…”

Section: History Of Tobacco Plant In Medicinementioning

confidence: 99%

“…tumor targeting or cancer treatment [23,24], prevention of tooth decay [25] and preventing sexually transmitted disease [26].…”

Section: The Pharmaceutical Benefits Of Tobacco Plantsmentioning

confidence: 99%

Tobacco plant: A possible key to Ebola vaccine

Zahara¹,

Bibi²,

Ajmal³

et al. 2017

JCLM

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“…A useful recent review details how plant-based antibody products may "…provide lower upfront cost, shorter time to clinical and market supply, and lower cost of goods (COGs)…[and] improvements in pharmacokinetics, safety and efficacy" [146]. As an object example, an important aspect of rabies disease prevention is therapy, given the many people in developing countries who get bitten by suspected rabid animals annually -and a major development in this area is the production of potent rabies-neutralising antibodies in plants, given the prevailing situation of mainly equine-produced sera being in short supply and of variable quality.…”

Section: Anti-viral Therapeutic Antibodiesmentioning

confidence: 99%

Plant-based vaccines against viruses

Rybicki

2014

Virology Journal

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Plant-made or "biofarmed" viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.

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Emerging Antibody-based Products

Cited by 15 publications

References 53 publications

Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge

Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge

Tobacco plant: A possible key to Ebola vaccine

Plant-based vaccines against viruses

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