Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.
Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.
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DOI：
10.1371/journal.pone.0043845
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Guo Y
中科院分区：
文献类型：
--
作者：
Chen C;Wang S;Wang H;Mao X;Zhang T;Ji G;Shi X;Xia T;Lu W;Zhang D;Dai J;Guo Y
肉毒杆菌神经毒素（BoNT）是危及生命的人类疾病肉毒中毒的病原体，已被认为是生物战剂。单克隆抗体 (mAb) 疗法作为 BoNT 疗法具有相当大的前景，但 mAb 对抗 BoNT 的效力通常低于多克隆抗体（或寡克隆抗体）。迫切需要通过开发有效的单克隆抗体来确认关键表位。我们从一组针对 BoNT/B 的中和抗体中选择了 3 种识别 BoNT/B 不同非重叠表位的中和 mAb。通过比较不同组合组之间的中和效果，我们发现对神经节苷脂受体结合位点作出反应的8E10可以与5G10和2F4协同作用，识别Syt II结合位点内的非重叠表位。然而，5G10与2F4阻断蛋白受体结合位点的组合并没有达到协同效应。此外，我们发现8E10的结合表位在BoNT A、B、E和F中是保守的，这可能在体内交叉保护不同血清型BoNT的攻击。识别 BoNT 中不同受体结合域的两种 mAb 的组合具有协同效应。 8E10 是与其他针对其他血清型 BoNT 中蛋白质受体结合域的 mAb 协同组合的潜在通用伙伴。
Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo. The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.
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影响因子：
56.9
作者：
Dong, M;Yeh, F;Chapman, ER
通讯作者：
Chapman, ER
影响因子：
2.9
作者：
Fu, Zhuji;Chen, Chen;Barbieri, Joseph T.;Kim, Jung-Ja P.;Baldwin, Michael R.
通讯作者：
Baldwin, Michael R.
DOI：
10.1073/pnas.0609713104
发表时间：
2007-01-02
影响因子：
11.1
作者：
Rummel, Andreas;Eichner, Timo;Binz, Thomas
通讯作者：
Binz, Thomas
影响因子：
4.4
作者：
Perosa, F;Luccarelli, G;Dammacco, F
通讯作者：
Dammacco, F
影响因子：
5.4
作者：
KIENLE, E;BUSCHMANN, HG
通讯作者：
BUSCHMANN, HG