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RiVax是一种重组蓖麻毒素亚单位疫苗,可保护小鼠免受经口或气溶胶途径给予的蓖麻毒素侵害。

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

作者信息

Smallshaw Joan E, Richardson James A, Vitetta Ellen S

机构信息

The Cancer Immunobiology Center and the Department of Microbiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8576, USA.

出版信息

Vaccine. 2007 Oct 16;25(42):7459-69. doi: 10.1016/j.vaccine.2007.08.018. Epub 2007 Aug 30.

DOI:10.1016/j.vaccine.2007.08.018
PMID:17875350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2049008/
Abstract

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.

摘要

蓖麻毒素是一种植物毒素,属于美国疾病控制与预防中心(CDC)的B级生物威胁物质。我们的重组蓖麻毒素A链疫苗(RiVax)在两个已知毒性位点均含有突变,在剂量至少为免疫原性剂量800倍时无残留毒性。肌肉注射(i.m.)无佐剂的RiVax可保护小鼠免受腹腔注射蓖麻毒素的侵害。此外,不含明矾的该疫苗在人类志愿者中是安全且具有免疫原性的。在此我们描述了小鼠灌胃和雾化蓖麻毒素攻击模型的建立,并证明肌肉注射疫苗可保护小鼠免受通过这两种途径递送的蓖麻毒素的侵害。此外,通过组织学和肺功能测试确定,RiVax还可预防雾化诱导的肺损伤。

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本文引用的文献

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Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage.高剂量蓖麻毒素的肺内给药会引发全身炎症反应和肾小球损伤。
Am J Pathol. 2007 May;170(5):1497-510. doi: 10.2353/ajpath.2007.060703.
2
Evidence for widespread epithelial damage and coincident production of monocyte chemotactic protein 1 in a murine model of intestinal ricin intoxication.在小鼠肠道蓖麻毒素中毒模型中广泛上皮损伤及单核细胞趋化蛋白1同时产生的证据。
Infect Immun. 2007 Apr;75(4):1745-50. doi: 10.1128/IAI.01528-06. Epub 2007 Feb 5.
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A pilot clinical trial of a recombinant ricin vaccine in normal humans.重组蓖麻毒素疫苗在正常人体中的初步临床试验。
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2268-73. doi: 10.1073/pnas.0510893103. Epub 2006 Feb 3.
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Humoral immune defense (antibodies): recent advances.体液免疫防御(抗体):最新进展
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Ricin poisoning: a comprehensive review.蓖麻毒素中毒:全面综述
JAMA. 2005 Nov 9;294(18):2342-51. doi: 10.1001/jama.294.18.2342.
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Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin.抗蓖麻毒素重组蛋白疫苗RiVax的临床前毒性和疗效测试。
Vaccine. 2005 Sep 15;23(39):4775-84. doi: 10.1016/j.vaccine.2005.04.037.
7
Impact of cethromycin (ABT-773) therapy on microbiological, histologic, immunologic, and respiratory indices in a murine model of Mycoplasma pneumoniae lower respiratory infection.在肺炎支原体下呼吸道感染小鼠模型中,塞托霉素(ABT - 773)治疗对微生物学、组织学、免疫学和呼吸指标的影响
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Insertional mutagenesis of ricin A chain: a novel route to an anti-ricin vaccine.蓖麻毒素A链的插入诱变:一种新型抗蓖麻毒素疫苗的研发途径。
Vaccine. 2004 Jul 29;22(21-22):2800-5. doi: 10.1016/j.vaccine.2004.01.024.
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Ricin: mechanism of toxicity, clinical manifestations, and vaccine development. A review.蓖麻毒素:毒性机制、临床表现及疫苗研发。综述。
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Finding a new vaccine in the ricin protein fold.在蓖麻毒素蛋白结构域中寻找新型疫苗。
Protein Eng Des Sel. 2004 Apr;17(4):391-7. doi: 10.1093/protein/gzh043. Epub 2004 Jun 8.