Immunochemistry Laboratory, Butantan Institute, São Paulo 05503-900, Brazil.
Laboratory of Structure and Function of Biomolecules, Butantan Institute, São Paulo 05503-900, Brazil.
Toxins (Basel). 2023 Sep 20;15(9):584. doi: 10.3390/toxins15090584.
Accidents with snakes are responsible for about 32,000 deaths annually in sub-Saharan Africa, caused mostly by snakes from the genus , in particular . venom is composed of a complex mixture of toxins, mainly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. In this work, we compared two approaches to anti-. antivenom production: immunization with crude snake venom ("traditional approach") and immunization with selected key toxins isolated from the snake venom ("toxin oriented" approach). Fractions from venom were isolated by size exclusion chromatography. Crude venom and samples containing serine proteases or metalloproteases were selected for the immunization of BALB/c mice. Anti- and anti-serine proteases plasmas showed a similar recognition profile and higher titers and affinity than the anti-metalloproteases plasma. Cross-recognition of other venoms was observed, but with low intensity. Although the plasma of all experimental groups inhibited the enzymatic activity of venom in vitro, in vivo protection was not achieved. Our results have shown limitations in both approaches considered. Based on this, we proposed a model of polyclonal, species-specific, monovalent antivenoms that could be used as a base to produce customizable polyvalent sera for use in sub-Saharan Africa.
在撒哈拉以南非洲，每年约有 32,000 人因蛇伤而死亡，这些蛇伤主要是由 属的蛇引起的，尤其是 。毒液由复杂的毒素混合物组成，主要有金属蛋白酶、丝氨酸蛋白酶、磷脂酶、凝集素和整联蛋白。在这项工作中，我们比较了两种抗蛇毒血清生产方法：用粗蛇毒免疫（“传统方法”）和从蛇毒中分离出的选定关键毒素免疫（“毒素导向方法”）。 毒液通过排阻色谱法分离成不同的组分。选择含有丝氨酸蛋白酶或金属蛋白酶的粗毒液和样品进行 BALB/c 小鼠免疫。抗-和抗丝氨酸蛋白酶的血浆表现出相似的识别谱和更高的效价和亲和力，比抗金属蛋白酶的血浆高。观察到对其他 毒液的交叉识别，但强度较低。尽管所有实验组的血浆都能抑制 毒液在体外的酶活性，但未能实现体内保护。我们的结果表明，所考虑的两种方法都存在局限性。基于此，我们提出了一种多克隆、种特异性、单价抗蛇毒血清的模型，可作为生产针对撒哈拉以南非洲地区的可定制多价血清的基础。
