Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin

Smallshaw, Joan E.; Richardson, James A.; Pincus, Seth H.; Schindler, John; Vitetta, Ellen S.

doi:10.1016/j.vaccine.2005.04.037

Cited by 72 publications

(82 citation statements)

References 16 publications

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“…The construction, production and purification of RiVax have been described [ 9,10 ]. Briefly, the gene for the enzymatically active wild type RTA, kindly provided by Dr. J. Michael Lord, Department of Biology Sciences, University of Warwick, Coventry, U.K. [ 13,14 ], was genetically altered to eliminate both its cytotoxic activity (Y80A) and its ability to induce vascular leak (V76M).…”

Section: Vaccine Ricin and Antibodiesmentioning

confidence: 99%

“…This preparation was formulated at 0.2 mg/mL in PBS with 0.1 M sucrose (USP, JTBaker, Phillipsburg, NJ) and 0.04% polysorbate (Tween) 80 (USP, JTBaker), pH 7.4, then vialed, plugged, sealed, labeled, and frozen at -80°C. Periodically stability analysis of this material was performed [ 10 ]. Alternately, it was formulated in 10 mM Histidine-HCl, 144 mM NaCl, pH 6.0, 50% v/ v glycerol, stored at -20°C, which has been determined to be an ideal formulation for stability (Dr. Russ Middaugh, personal communication).…”

Section: Vaccine Ricin and Antibodiesmentioning

confidence: 99%

“…ribotoxicity and vascular leak-inducing ability [9][10]. This vaccine, in the absence of adjuvant, is non-toxic and immunogenic in mice, rabbits and humans [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

Smallshaw

Richardson

Vitetta

2007

Vaccine

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120

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Ricin is a plant toxin that is a CDC level B biothreat. Our recombinant ricin A chain vaccine (RiVax), which contains mutations in both known toxic sites, has no residual toxicity at doses at least 800 times the immunogenic dose. RiVax without adjuvant given intramuscularly (i.m.) protected mice against intraperitoneally administered ricin. Furthermore the vaccine without alum was safe and immunogenic in human volunteers. Here we describe the development of gavage and aerosol ricin challenge models in mice and demonstrate that i.m. vaccination protects mice against ricin delivered by either route. Also RiVax protects against aerosol-induced lung damage as determined by histology and lung function tests.

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Section: Vaccine Ricin and Antibodiesmentioning

confidence: 99%

Section: Vaccine Ricin and Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

Smallshaw

Richardson

Vitetta

2007

Vaccine

Self Cite

120

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“…There is no approved vaccine for ricin, and a lethal dose kills within a few days. We have previously described a recombinant RTA vaccine (15,16) in which two amino acids in the protein have been genetically altered to inactivate both the ribotoxic (8,12,13) and vascular leak syndrome (VLS)-inducing sites (1). The mutant protein, Y80A/ V76M or RiVax, retains all the immunodominant epitopes recognized by a panel of monoclonal antibodies (MAbs) (16).…”

mentioning

confidence: 99%

“…We have previously described a recombinant RTA vaccine (15,16) in which two amino acids in the protein have been genetically altered to inactivate both the ribotoxic (8,12,13) and vascular leak syndrome (VLS)-inducing sites (1). The mutant protein, Y80A/ V76M or RiVax, retains all the immunodominant epitopes recognized by a panel of monoclonal antibodies (MAbs) (16). In addition, the crystal structure of RiVax revealed no significant perturbation in the molecule (9), and all known immunodominant linear B cell and HLA class II-restricted T cell epitopes were retained (3,18).…”

mentioning

confidence: 99%

Pilot Phase IB Clinical Trial of an Alhydrogel-Adsorbed Recombinant Ricin Vaccine

Vitetta

Smallshaw

Schindler

2012

Clin. Vaccine Immunol.

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Ricin Poisoning

Audi¹,

Belson²,

Patel³

et al. 2005

JAMA

566

292

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ROWING AWARENESS AND concern about ricin, a potent biologic toxin, as a possible terrorist weapon has necessitated a comprehensive review of this poison. 1 The Centers for Disease Control and Prevention (CDC) categorizes ricin as a Category B agent (second-highest priority), as it is moderately easy to disseminate, resulting in low mortality but moderate to high morbidity, and requires specific enhancement of the CDC's diagnostic and disease surveillance capacity. 2 Such agents are not routinely encountered, so heightened awareness in the health care community and a strong public health infrastructure are necessary for detection and response. We therefore have summarized the literature on ricin poisoning and provided recommendations for clinicians and public health professionals dealing with a ricin attack against a civilian population. EVIDENCE ACQUISITION Using PubMed, we searched MEDLINE and OLDMEDLINE databases from January 1950 to August 2005 using the keywords ricin, ricinus communis, ricinine, plant toxins, castor beans, castor dust, and castor oil. Keywords were used alone and with the modifiers toxicity, poisoning, diagnosis, clinical effects, treatment , warfare, chemical terrorism, and weapon. The Chemical and Biological Information Analysis Center (http: //www.cbiac.apgea.army.mil) database was searched for historical and military literature related to ricin tox-CME available online at www.jama.com Context The recent discoveries of ricin, a deadly biologic toxin, at a South Carolina postal facility, a White House mail facility, and a US senator's office has raised concerns among public health officials, physicians, and citizens. Ricin is one of the most potent and lethal substances known, particularly when inhaled. The ease with which the native plant (Ricinus communis) can be obtained and the toxin extracted makes ricin an attractive weapon. Objectives To summarize the literature on ricin poisoning and provide recommendations based on our best professional judgment for clinicians and public health officials that are faced with deliberate release of ricin into the environment. Literature Acquisition Using PubMed, we searched MEDLINE and OLDMEDLINE databases (January 1950-August 2005). The Chemical and Biological Information Analysis Center database was searched for historical and military literature related to ricin toxicity. Book chapters, unpublished reports, monographs, relevant news reports, and Web material were also reviewed to find nonindexed articles. Results Most literature on ricin poisoning involves castor bean ingestion and experimental animal research. Aerosol release of ricin into the environment or adulteration of food and beverages are pathways to exposure likely to be exploited. Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse. Inhalation (onset of symptoms is likely within 8 hou...

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Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin

Cited by 72 publications

References 16 publications

RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

Pilot Phase IB Clinical Trial of an Alhydrogel-Adsorbed Recombinant Ricin Vaccine

Ricin Poisoning

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