Ricin immunization

Drugs Available (No specific anti-toxin) Active immunization and passive antibody prophylaxis are under study, as both are effective in protecting animals from death following exposure by intravenous or respiratory routes. Ricin is not dermally active therefore, respiratory protection is the most critical means of prevention. 

Abrin, from jequirity beans (Abrus precatorius), resembles ricin so closely in its action that the difference was established only when it was noted that immunity against one did not constitute immunity against the other. 

Candidate vaccines under development are immunogenic and confer protection against lethal aerosol exposures. Recent animal studies have shown that either active immunization or passive prophylaxis may be effective against intravenous or intraperitoneal intoxication with ricin (Poh et al, 1994). In the case of inhalational exposure, active immunization or prophylactic administration of aerosolized specific anti-ricin antibody may also be effective (Poli et al, 1994). Unfortunately, these applications may not be clinically available since they are still under investigation. 

Lemley, P.V., Wright, D.C. (1991). Active immunization after passive monoclonal antibody and ricin toxin challenge (abstract 029), 10th World Congress on Animal, Plant, and Microbial Toxins. Singapore, China. 

Analytical methods include immune methods (ELISA) and liquid chromatography/mass spectrometry (LC/MS). Gastric contents can be assayed and ricin can be detected in blood and body fluids by radioimmunoassay and LC/MS (Darby et al, 2001 Mouser et al, 2007). 

Figure 3.9 The persistent IgE response induced by repeated immunization of Brown Norway and Wistar rats with ricin and antigen.

Ricin s potent immogenicity raises hope for development of an effective vaccine (36). Animal studies reveal that either active or passive immunization may be effective for intravenous or intraperitoneal exposures but only if given within a few... 

Although it is less common than is the castor seed allergic syndrome, workers chronically exposed to subacute ricin or other RIPs may develop Type I allergies directly against the toxins allergies to purified RIPs can be demonstrated by immune sensitization and IgE induction (Hunt et al., 1918 Forster-Waldl et al., 2003 Szalai et al., 2005). 

Griffiths, G.D., Bailey, S.C., Hambrook, J.L., Keyte, M., Jayasekera, P., Miles, J. and Williamson, E. (1997) Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin. Vaccine, 15, 1933-1939. 

Kende, M., Yan, C., Hewetson, J., Frick, M.A., Rill, W.L. and Tammariello, R. (2002) Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge. Vaccine, 20, 1681-1691. 

Lemley, P.V. and Creasia, D.A. (1995) USA 5,453,271, Vaccine against Ricin Toxin. September 26, 1995. Lemley, P.V. and Wright, D.C. (1992) Mice are actively immunized after passive monoclonal antibody... 

Li, X.P., Baricevic, M., Saidasan, H. and Turner, N.E. (2006) Ribosome depurination is not sufficient for ricin mediated cell death in Saccharomyces cerevisiae. Infect Immun, 75(1), 417-427. 

Teter, K. and Holmes, R.K. (2002) Inhibition of endoplasmic reticulum-associated degradation in CHO cells resistant to cholera toxin. Pseudomonas aeruginosa exotoxin A, and ricin. Infect Immun, 70, 6172-6179. 

Active immunization with ricin toxoid is designed to provide long-lasting protection against a subsequent ricin challenge. Since inhalation... 

A potential problem with ricin toxoid immunization is that at least some preparations have shown a tendency to revert to the toxic form when stored at room temperature or 4°C (Griffiths et al, 1998). This has led to the examination of different vaccination candidates based upon ricin A chain (Griffiths et al, 1998). The challenge is to develop a ricin A chain derivative that is sufficiently immunogenic to be used as a vaccine without having the enzymatic activity of the complete ricin A chain molecule. 

Other investigators (Marsden et al, 2004) introduced an inhibitor peptide into the ricin A chain which completely eliminated the in vivo cy-totoxicty of the protein, was non-toxic when injected into rats and elicited an immune response that protected the animals from an intratracheal ricin dose of five times the LD50. Most recently, a fragment of the ricin A chain has been identified which has no enzymic activity, does not induce vascular leak syndrome, is very stable and completely protects mice from subsequent exposure to a lethal ricin challenge when the toxin is administered either by intraperitoneal injection or whole-body aerosol exposure (Olsen et al, 2004 Lebeda and Olson, 1999 McHugh et al, 2004). 

SPR is a representative physical phenomenon that is widely utilized for label-free characterization of molecules on thin metal films. The basic principle and operation of SPR has been described in more detail in several review articles [77, 78]. The reports on SPR-based immune sensors have steeply increased for detection of analytes with low molecular weights in recent years. SPR detection in microfluidic systems can provide various advantages. Immunoreactions are completed within a short time due to small sample volumes down to the nanolitre scale. Kim et al. developed a simple and versatile miniaturized SPR immunosensor enabling parallel analyses of multiple analytes [79]. Their SPR sensor was claimed to exhibit good stability and reusability for 40 cycles and more than 35 days. Feltis et al. demonstrated a low-cost handheld SPR-based immunosensor for the toxin Ricin [80]. Springer et al. reported a dispersion-free microfluidic system with a four-channel SPR sensor platform, which considerably improved the response time and sensitivity [81]. The sensor was able to detect short sequences of nucleic acids down to a femtomole level for 4 min. Waswa et al. demonstrated the immunological detection of E. coli 0157 H7 in milk, apple juice, and meat juice extracted from... 

Action on Blood — in vitro, ricin hemolyzes and agglutinates the corpuscles of nearly all warm-blooded animals (Stillmark, 1886). The agglutination does not seem to occur in the body, but is of great importance as an immunity phenomenon. Leucocytes, epithelial and other cells (except those with thick membranes, as yeast) are also agglutinated as likewise the stroma of laked corpuscles (Elfstrand). The presence of serum hinders the effect. 

Antiridn — Injections of the phytotoxins produce typical antitoxins, so that an immunized animal can survive 5,000 ordinary fatal doses of ricin. Some of the basic work of Ehrlich was done with ricin and abrin. He showed 11891) that the immunity starts in five to six days, and lasts six or seven months. The resistance of the corpuscles is unchanged, the antiricin being contained in the peeudoglobulin fraction of the serum (Jacoby, 1902). It contains amitoxin, antiagglutinin (probably identical) and precipitin. Mad-sac and Walbum found that this combination obeys the same laws as diphtheria antitoxin. The toxicity of ricin is modified rather complexly by lecithin (Lawrow, 1913). 

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