A novel recombinant vaccine which protects mice against ricin intoxication

Smallshaw, Joan E.

doi:10.1016/s0264-410x(02)00312-2

Cited by 104 publications

(104 citation statements)

References 15 publications

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“…The data are shown in Figure 2. There was very little overlap between the lethal and 'safe' doses, and the estimated LD 50 of ricin in mice was approximately 4 μg/kg, in agreement with the published value of 3-5 μg/kg [ 9 ]. Histopathological analysis of the lungs (including the trachea and alveoli) from the mice showed necrosis of alveolar cells, indicating that the aerosol particles were small enough (1-2 μm) to penetrate to the aveolar region of the lung [ 20 ] (data not shown).…”

Section: The Aerosol Challenge Routesupporting

confidence: 86%

“…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%

“…The LD 50 dose was determined as described [ 9 ]. For all i.p challenges with ricin, mice were injected with ricin in a volume of 100 μL PBS, monitored and weighed daily for 14 days, and euthanized by CO 2 asphyxiation followed by spinal dislocation when moribund or following 25% weight loss.…”

Section: Determination Of the Ld 50 Of Ricin Delivered By Ip Injectionmentioning

confidence: 99%

“…This value was over three logs lower than the reported dose of 20 mg/kg [ 19 ], and the same as our LD 50 dose of ricin by i.p. injection [ 9 ]. With our newly established fasting/challenge regimen, we challenged groups of three mice with 10 μg, 100 μg, 1 mg, or 10 mg ricin per kg, (corresponding to 1, 10, 100, or 1,000 times our LD 50 ) and examined the duodenum for tissue damage 18 hours post-challenge.…”

Section: The Intragastric Gavage Challenge Routementioning

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

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: The Aerosol Challenge Routesupporting

confidence: 86%

Section: Vaccine Ricin and Antibodiesmentioning

confidence: 99%

Section: Determination Of the Ld 50 Of Ricin Delivered By Ip Injectionmentioning

confidence: 99%

Section: The Intragastric Gavage Challenge Routementioning

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%

See 3 more Smart Citations

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

Smallshaw

Richardson

Vitetta

2007

Vaccine

120

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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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