Gal Yoav, Sapoznikov Anita, Falach Reut, Mazor Ohad, Alcalay Ron, Elhanany Eytan, Aftalion Moshe, Ehrlich Sharon, Kronman Chanoch, Sabo Tamar
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
Antibodies (Basel). 2020 Feb 6;9(1):4. doi: 10.3390/antib9010004.
Abrin and ricin are potent AB toxins, which are considered biological threats. To date, there are no approved treatments against abrin or ricin intoxications. Previously, we showed that the administration of polyclonal anti-abrin antibodies to mice that were intranasally exposed to abrin, even very late post-exposure, conferred an exceedingly high-level of protection, while following ricin intoxication, similar treatment with anti-ricin antibodies resulted in negligible survival rates. To probe this unexpected difference in protection ability, we first examined whether the efficient anti-abrin-induced protection was due to neutralization of the A-subunit responsible for the catalytic effect, or of the B-subunit, which enables binding/internalization, by evaluating the protection conferred by antibodies directed against one of the two subunits. To this end, we generated and immunized rabbits with chimeric toxins containing a single abrin subunit, AB in which abrin A-subunit was linked to ricin B-subunit, and AB in which ricin A-subunit is linked to abrin B-subunit. Here, we show that antibodies raised against either AB or AB conferred exceptionally high protection levels to mice following intranasal exposure to a a lethal dose of abrin, suggesting that the high level of protection conferred by anti-abrin antibodies is not related to the neutralization of a particular subunit.
相思子毒素和蓖麻毒素是强效AB毒素,被视为生物威胁。迄今为止,尚无针对相思子毒素或蓖麻毒素中毒的获批治疗方法。此前,我们发现,给经鼻暴露于相思子毒素的小鼠注射多克隆抗相思子毒素抗体,即使在暴露后很晚的时间给药,也能提供极高水平的保护,而在蓖麻毒素中毒后,用抗蓖麻毒素抗体进行类似治疗的存活率却微乎其微。为探究这种保护能力的意外差异,我们首先通过评估针对两个亚基之一的抗体所提供的保护,来检查高效抗相思子毒素诱导的保护是否归因于对负责催化作用的A亚基或使结合/内化的B亚基的中和作用。为此,我们制备了含有单个相思子毒素亚基的嵌合毒素,并将其免疫兔子,这些嵌合毒素包括将相思子毒素A亚基与蓖麻毒素B亚基相连的AB,以及将蓖麻毒素A亚基与相思子毒素B亚基相连的AB。在此,我们表明,针对AB或AB产生的抗体在小鼠经鼻暴露于致死剂量的相思子毒素后,能为其提供极高的保护水平,这表明抗相思子毒素抗体提供的高水平保护与特定亚基的中和作用无关。