Harrison R A, Hasson S S, Harmsen M, Laing G D, Conrath K, Theakston R D G
Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
Toxicon. 2006 Mar;47(3):364-8. doi: 10.1016/j.toxicon.2005.10.017. Epub 2005 Dec 15.
Envenoming by snakes results in severe systemic and local pathology. Intravenous administration of antivenom, prepared from IgG of venom immunised horses or sheep, is the only effective treatment of systemic envenoming. Conventional antivenoms, formulated as intact IgG, papain-cleaved (Fab) or pepsin-cleaved F(ab')2 fragments, are however ineffective against the local venom effects because of their inability to penetrate the blood/tissue barrier. We have embarked on a new research program to examine (i) whether the unusually small (15 kDa) antigen-binding fragment of camelid heavy chain IgG (V(H)H) can be exploited to neutralise the local effects of envenoming and (ii) whether a novel antivenom to treat both the systemic and local effects of envenoming can be formulated by combining anti-snake venom V(H)H and conventional F(ab')2. In this preliminary study, we demonstrate that camels and llamas respond to immunisation with Echis ocellatus venom with high antibody titres and broad antigen specificity. These encouraging immunological results were matched by the successful elimination of venom-induced haemorrhage by IgG from the venom-immunised camels and llamas. Unexpectedly, we report for the first time that camelid serum contains a non-IgG, highly potent inhibitor of venom-induced haemorrhage.
蛇毒咬伤会导致严重的全身和局部病理变化。静脉注射由经毒液免疫的马或羊的IgG制备的抗蛇毒血清,是治疗全身中毒的唯一有效方法。然而,传统的抗蛇毒血清,无论是完整的IgG、木瓜蛋白酶裂解的(Fab)还是胃蛋白酶裂解的F(ab')2片段,由于无法穿透血液/组织屏障,对局部毒液作用无效。我们已启动一项新的研究计划,以研究(i)骆驼科动物重链IgG(V(H)H)异常小的(15 kDa)抗原结合片段是否可用于中和中毒的局部作用,以及(ii)是否可以通过将抗蛇毒V(H)H与传统的F(ab')2结合来配制一种新型抗蛇毒血清,以治疗中毒的全身和局部作用。在这项初步研究中,我们证明骆驼和羊驼对用锯鳞蝰毒液免疫有高抗体滴度和广泛的抗原特异性反应。这些令人鼓舞的免疫学结果与用毒液免疫的骆驼和羊驼的IgG成功消除毒液诱导的出血相匹配。出乎意料的是,我们首次报告骆驼科动物血清中含有一种非IgG的、高效的毒液诱导出血抑制剂。