Sells P G, Jones R G, Laing G D, Smith D C, Theakston R D
Venom Research Unit, Liverpool School of Tropical Medicine, U.K.
Toxicon. 1994 Dec;32(12):1657-65. doi: 10.1016/0041-0101(94)90324-7.
Conventional treatment of Naja kaouthia (Thai cobra) envenoming requires large volumes (up to 600 ml) of equine antivenom, which results in a high incidence of serum reactions. The inefficiency of the antivenom is assumed to be related to the high percentage (approx. 20%) of alpha-neurotoxin, a relatively weak and highly toxic immunogen, present in the native venom. First, antibodies to N. kaouthia venom were raised in sheep, which protected mice against challenge with whole venom. Second, ovine antibodies to the purified neurotoxin and to three different neurotoxin conjugates were developed and their neutralising abilities against either whole venom or neurotoxin were compared using murine ED50 tests. High titre antibodies, assessed by enzyme immunoassay and Western blot, were obtained from all four neurotoxin immunisation regimens. Neurotoxin conjugated to rabbit anti-sheep IgG produced the highest titres against both neurotoxin and whole venom. This antiserum provided protection against neurotoxin challenge but failed to protect against whole venom. Furthermore, the addition of neurotoxin antibodies to whole venom antiserum did not enhance the neutralisation efficacy of the latter. These findings raise the possibility that in mice other toxins apart from the neurotoxin may significantly contribute to the lethal effect of N. kaouthia venom.
眼镜王蛇(泰国眼镜蛇)咬伤的传统治疗需要大量(高达600毫升)的马抗蛇毒血清,这导致血清反应的发生率很高。抗蛇毒血清的低效被认为与天然毒液中高比例(约20%)的α-神经毒素有关,α-神经毒素是一种相对较弱但毒性很强的免疫原。首先,在绵羊体内产生针对眼镜王蛇毒液的抗体,这些抗体可保护小鼠免受全毒液的攻击。其次,制备了针对纯化神经毒素和三种不同神经毒素偶联物的羊抗体,并使用小鼠半数有效剂量(ED50)试验比较它们对全毒液或神经毒素的中和能力。通过酶免疫测定和蛋白质印迹评估,从所有四种神经毒素免疫方案中都获得了高滴度抗体。与兔抗羊IgG偶联的神经毒素对神经毒素和全毒液产生的滴度最高。这种抗血清可保护小鼠免受神经毒素攻击,但不能保护小鼠免受全毒液攻击。此外,将神经毒素抗体添加到全毒液抗血清中并不能提高后者的中和效力。这些发现增加了一种可能性,即在小鼠中,除神经毒素外的其他毒素可能对眼镜王蛇毒液的致死作用有显著贡献。