Noy-Porat Tal, Alcalay Ron, Epstein Eyal, Sabo Tamar, Kronman Chanoch, Mazor Ohad
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona, Israel.
Toxicon. 2017 Mar 1;127:100-105. doi: 10.1016/j.toxicon.2017.01.009. Epub 2017 Jan 12.
The plant toxin ricin is considered a potential bioterror agent against which there is no available antidote. To date, neutralizing antibodies are the most promising post-exposure treatment for ricin intoxication, yet so far they were shown to be effective only when given within several hours post exposure. As part of an ongoing effort to develop efficient ricin-countermeasures, we tested whether high-affinity antibodies that were previously isolated from immunized non-human primates, may confer effective post-exposure therapy for ricin-intoxicated mice treated at late time-points after exposure. While each antibody is capable of providing high protection rate by itself, a formulation consisting of three neutralizing antibodies that target different epitopes was tested to provide therapeutic coverage against different variants of the malicious pathogen. Indeed, the tri-antibody based cocktail was highly effective, its administration resulting in very high survival rates (>70%) when animals were treated as late as 48 h post exposure and significant protection (>30%) even at 72 h. This study establishes for the first time that anti-ricin antibodies can serve as a highly effective antidote at such late time-points after exposure. From the clinical point of view, the extended therapeutic window documented here is of high importance allowing adequate time to accurately identify the causative agent and may permit initiation of life-saving treatment with these antibodies even after the onset of clinical signs.
植物毒素蓖麻毒素被认为是一种潜在的生物恐怖制剂，目前尚无可用的解毒剂。迄今为止，中和抗体是蓖麻毒素中毒暴露后最有前景的治疗方法，但到目前为止，仅在暴露后数小时内给予才显示有效。作为开发有效蓖麻毒素应对措施的一项持续努力的一部分，我们测试了先前从免疫的非人类灵长类动物中分离出的高亲和力抗体，对于暴露后晚期治疗的蓖麻毒素中毒小鼠是否可提供有效的暴露后治疗。虽然每种抗体本身都能够提供高保护率，但我们测试了一种由三种靶向不同表位的中和抗体组成的制剂，以提供针对恶意病原体不同变体的治疗覆盖。事实上，基于三抗体的混合物非常有效，当动物在暴露后48小时才接受治疗时，其给药导致非常高的存活率（>70%），甚至在72小时时也有显著保护作用（>30%）。这项研究首次证实，抗蓖麻毒素抗体在暴露后的此类晚期时间点可作为一种高效解毒剂。从临床角度来看，此处记录的延长治疗窗口非常重要，它允许有足够的时间准确识别病原体，甚至在临床症状出现后也可使用这些抗体启动挽救生命的治疗。
