Yamamoto Akihiko, Harano Satomi, Shinya Noriko, Nagano Ayataka, Miyatsu Yoshinobu, Sawabe Kyouko, Matsumura Takayuki, Ato Manabu, Takahashi Motohide, Taki Hisashi, Hifumi Toru
Division of Biosafety Control and Research, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.
J Toxicol Pathol. 2018 Apr;31(2):105-112. doi: 10.1293/tox.2017-0053. Epub 2018 Feb 19.
The redback spider () is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom's irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverse-effect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development.
红背蜘蛛（）并非日本本土物种，但现已在日本全国范围内扩散。其对人类的叮咬虽罕见，但可能致命。我们通过对马血浆进行免疫，制备了冻干红背蜘蛛抗毒血清，用于治疗日本境内的叮咬病例。本研究包括对抗毒血清的两项非临床测试：一项局部刺激性研究，对兔子进行单次肌肉注射（分别注射生理盐水和现有的冻干白喉抗毒素作为对照和比较物质）；另一项是对大鼠进行为期2周的重复间歇性静脉给药毒性研究。刺激性研究表明，在测试条件下，抗毒血清的刺激性与生理盐水和现有抗毒素制剂相当。在重复给药毒性研究中，未发现雄性或雌性大鼠有毒性变化，且判定雄性和雌性大鼠的无观察到不良反应水平（NOAEL）均为剂量体积20 mL/kg（抗毒血清活性1082单位/kg）。此外，蛋白质含量和添加剂组成相同的白喉抗毒素和红背蜘蛛抗毒血清在毒理学上没有差异。基于这些发现，我们将进一步推进红背蜘蛛抗毒血清临床应用的研究。本研究得到了日本医疗研究与开发机构新兴和再发传染病研究项目的支持。
