Understanding Ricin from a Defensive Viewpoint

Griffiths, Gareth

doi:10.3390/toxins3111373

Cited by 62 publications

(67 citation statements)

References 66 publications

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“…80 In vitro toxicity assays provide information on the type of toxic action but do not provide absolute evidence of which substance is present in the sample. 77 PCR-based methods detect the gene encoding the toxin but they do not provide evidence for the presence of the toxin itself. 77 The low molecular weight alkaloid ricinine has been used as a marker of ingestion of Ricinus material because it was easier to analyze than the protein ricin.…”

Section: Ricinmentioning

confidence: 99%

“…78,79 Traditionally, immunological methods have been used to detect ricin. 11,77 ELISAs can be very sensitive but are prone to nonspecific reactions, and they may give positive responses for related proteins like RCA and even denatured ricin lacking toxic activity. 80 In vitro toxicity assays provide information on the type of toxic action but do not provide absolute evidence of which substance is present in the sample.…”

Section: Ricinmentioning

confidence: 99%

“…There are many recipes in books and on the internet on how to purify ricin from castor beans. 77 The availability and ease of preparation make ricin a threat for military or terrorist use. Ricin is the only protein listed under the Chemical Weapons Convention, and it is also classified as a biological warfare agent.…”

Section: Ricinmentioning

confidence: 99%

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Mass Spectrometric Detection of Protein-Based Toxins

Åberg

Björnstad

Hedeland

2013

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

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This review focuses on mass spectrometric detection of protein-based toxins, which are among the most toxic substances known. Special emphasis is given to the bacterial toxins botulinum neurotoxin from Clostridium botulinum and anthrax toxins from Bacillus anthracis as well as the plant toxin ricin produced by Ricinus communis. A common feature, apart from their extreme toxicity, is that they are composed of 2 polypeptide chains, one of which is responsible for cell uptake and another that has enzymatic function with the ability to destroy basic cellular functions. These toxins pose a threat, both regarding natural spread and from a terrorism perspective. In order for public health and emergency response officials to take appropriate action in case of an outbreak, whether natural or intentional, there is a need for fast and reliable detection methods. Traditionally, large molecules like proteins have been detected using immunological techniques. Although sensitive, these methods suffer from some drawbacks, such as the risk of false-positives due to cross-reactions and detection of inactive toxin. This article describes recently developed instrumental methods based on mass spectrometry for the reliable detection of botulinum neurotoxins, anthrax toxins, and ricin. Unequivocal identification of a protein toxin can be carried out by mass spectrometry-based amino acid sequencing. Furthermore, in combination with antibody affinity preconcentration and biochemical tests with mass spectrometric detection demonstrating the toxin's enzymatic activity, very powerful analytical methods have been described. In conclusion, the advent of sensitive, easily operated mass spectrometers provides new possibilities for the detection of protein-based toxins.

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Section: Ricinmentioning

confidence: 99%

Section: Ricinmentioning

confidence: 99%

See 1 more Smart Citation

Mass Spectrometric Detection of Protein-Based Toxins

Åberg

Björnstad

Hedeland

2013

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

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“…Ricin is a potent toxin with an aerosol LD 50 of 3 -5 µg/kg in mice [76]. While exposure to environmental ricin is unlikely, there is currently no approved antidote and its potential as a biological weapon make it a significant therapeutic target.…”

Section: Ricinmentioning

confidence: 99%

Polymer antidotes for toxin sequestration

Weisman

Chou

O’Brien

et al. 2015

Advanced Drug Delivery Reviews

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“…icin is one of a small group of plant and bacterial toxins that are classified at the domestic and international levels as potential agents of bioterrorism (1,2). Ricin is a product of castor beans (Ricinus communis), which are cultivated globally for their oils that are used in industrial lubricants, cosmetics, and biofuels.…”

mentioning

confidence: 99%

High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine

Toth

Angalakurthi

Slyke

et al. 2017

Clin Vaccine Immunol

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RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's ␣-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the "back side" (relative to the active site pocket) of RiVax. One subcluster involved ␣-helix A (residues 14 to 24) and ␣-helices F-G (residues 184 to 207); the other encompassed ␤-strand d (residues 62 to 69) and parts of ␣-helices D-E (154 to 164) and the intervening loop. Cluster III involved ␣-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a highresolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.KEYWORDS antibody, biodefense, epitope, mass spectrometry, toxin, vaccine R icin is one of a small group of plant and bacterial toxins that are classified at the domestic and international levels as potential agents of bioterrorism (1, 2). Ricin is a product of castor beans (Ricinus communis), which are cultivated globally for their oils that are used in industrial lubricants, cosmetics, and biofuels. The toxin itself is an ϳ65-kDa glycoprotein that makes up ϳ5% of the dry weight of a castor bean. The toxin can be purified by relatively simple affinity chromatography (3, 4). On a cellular level, ricin exerts its cytotoxic effects through ribosome inactivation and triggering of programmed cell death (5). Ricin's binding subunit, ricin toxin B subunit (RTB), is a galactose/N-acetyl galactosamine (Gal/GalNAc)-specific lectin that promotes toxin entry into mammalian cells, while ricin's enzymatic subunit, RTA, is an RNA N-glycosidase (EC 3.2.2.22) that, when successfully delivered into the cytoplasm, cleaves the sarcin-ricin

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Understanding Ricin from a Defensive Viewpoint

Cited by 62 publications

References 66 publications

Mass Spectrometric Detection of Protein-Based Toxins

Mass Spectrometric Detection of Protein-Based Toxins

Polymer antidotes for toxin sequestration

High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine

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