Localization of the sites and characterization of the mechanisms by which anti-light chain antibodies neutralize the actions of the botulinum holotoxin.
Localization of the sites and characterization of the mechanisms by which anti-light chain antibodies neutralize the actions of the botulinum holotoxin.
复制标题
抗轻链抗体中和肉毒杆菌全毒素作用的位点定位和机制表征。
DOI：
10.1016/j.vaccine.2009.02.051
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发表时间：
2009
期刊：
影响因子：
5.5
通讯作者：
Simpson,LanceL
中科院分区：
文献类型：
--
作者：
Takahashi,Tsuyoshi;Joshi,SureshG;Al-Saleem,Fetweh;Ancharski,Denise;Singh,Ajay;Nasser,Zidoon;Simpson,LanceL
A 型肉毒杆菌毒素的重组催化活性轻链被评估为潜在的候选疫苗。此前的研究表明，轻链可以在体内引发保护性免疫。 [基亚特金 N、马克西莫维奇 AB、辛普森 LL。通过口服重组肉毒杆菌毒素诱导免疫反应。 Infect Immun 1997;65(11):4586–91]，但这一观察结果的根本基础尚未确定。在本研究中，针对轻链的抗体被证明可以在体内的三个不同位点发挥作用，产生中和作用。首先，这些抗体可以阻止毒素吸收到体内。这在体外、毒素跨上皮单层结合和转运的研究以及体内吸入中毒的研究中得到了证明。其次，抗轻链抗体可促进毒素从体循环中清除。这在体内血液中毒素水平的研究以及肝脏和脾脏中毒素积累的平行研究中得到了证明。最后，抗轻链抗体可以保护胆碱能神经免受肉毒杆菌毒素的影响。这在两种类型的体外测定中得到了证明：鼠膈神经-半膈制剂的麻痹率和与 Neuro-2a 细胞的结合程度。综合起来，这些数据表明抗轻链抗体可以产生针对肉毒杆菌毒素的三层保护。
The recombinant, catalytically active light chain of botulinum toxin type A was evaluated as a potential vaccine candidate. Previous studies have shown that the light chain can elicit protective immunity in vivo. [Kiyatkin N, Maksymowych AB, Simpson LL. Induction of immune response by oral administration of recombinant botulinum toxin. Infect Immun 1997;65(11):4586–91], but the underlying basis for this observation was not determined. In the present study, antibodies directed against the light chain were shown to act at three different sites in the body to produce neutralization. Firstly, these antibodies acted to block toxin absorption into the body. This was demonstrated in vitro, in studies on binding and transport of toxin across epithelial monolayers, and in vivo, in studies on inhalation poisoning. Secondly, anti-light chain antibodies acted to promote clearance of toxin from the general circulation. This was demonstrated in vivo in studies on toxin levels in blood and in parallel studies on toxin accumulation in liver and spleen. Finally, anti-light chain antibodies acted to protect cholinergic nerves from botulinum toxin action. This was demonstrated in two types of in vitro assays: rate of paralysis of murine phrenic nerve-hemidiaphragm preparations and extent of binding to Neuro-2a cells. When taken together, these data show that anti-light chain antibodies can evoke three layers of protection against botulinum toxin.