Division of Infectious Disease, Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA.
Vaccine. 2011 Jan 17;29(4):681-9. doi: 10.1016/j.vaccine.2010.11.030. Epub 2010 Nov 27.
The RNA N-glycosidase ribosome inactivating proteins (RIPs) constitute a ubiquitous family of plant- and bacterium-derived toxins that includes the category B select agents ricin, abrin and shiga toxin. While these toxins are potent inducers of intestinal epithelial cell death and inflammation, very little is known about the mechanisms underlying mucosal immunity to these toxins. In the present study, we report that secretory IgA (SIgA) antibodies are not required for intestinal immunity to ricin, as evidenced by the fact that mice devoid of SIgA, due to a mutation in the polymeric immunoglobulin receptor, were impervious to the effects of intragastric toxin challenge following ricin toxoid immunization. Furthermore, parenteral administration of ricin-specific monoclonal IgGs, directed against either ricin's enzymatic subunit (RTA) or ricin's binding subunit (RTB), to wild type mice was as effective as monoclonal IgAs with comparable specificities in imparting intestinal immunity to ricin. These data are consistent with reports from others demonstrating that immunization of mice by routes known not to induce mucosal antibody responses (e.g., intramuscular and intradermal) is sufficient to elicit protection against both systemic and mucosal ricin challenges.
RNA N-糖苷酶核糖体失活蛋白(RIPs)构成了一类普遍存在的植物和细菌来源的毒素家族,其中包括 B 类选择剂蓖麻毒素、相思豆毒素和志贺毒素。虽然这些毒素是肠道上皮细胞死亡和炎症的有效诱导剂,但对于这些毒素的黏膜免疫机制知之甚少。在本研究中,我们报告说分泌型 IgA(SIgA)抗体不是对蓖麻毒素的肠道免疫所必需的,这一事实证明,由于聚合免疫球蛋白受体发生突变,缺乏 SIgA 的小鼠对胃内毒素挑战具有抗药性,即使在接受蓖麻毒素类毒素免疫接种后也是如此。此外,将针对蓖麻毒素的酶亚基(RTA)或结合亚基(RTB)的特异性单克隆 IgG 经肠胃外途径给予野生型小鼠,与具有类似特异性的单克隆 IgA 一样有效,可赋予小鼠对蓖麻毒素的肠道免疫力。这些数据与其他报告一致,表明通过已知不会诱导黏膜抗体反应的途径(例如肌肉内和皮内)对小鼠进行免疫接种足以引发针对全身和黏膜蓖麻毒素挑战的保护。