Exceptionally potent cross-reactive neutralization of Nipah and Hendra viruses by a human monoclonal antibody
Exceptionally potent cross-reactive neutralization of Nipah and Hendra viruses by a human monoclonal antibody
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DOI：
10.1086/528801
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发表时间：
2008-03-15
影响因子：
6.4
通讯作者：
Dimitrov, Dimiter S.
中科院分区：
文献类型：
--
作者：
Zhu, Zhongyu;Bossart, Katharine N.;Dimitrov, Dimiter S.
我们以前已经确定了中和人单克隆抗体对尼帕病毒（NiV）和亨德拉病毒（HeV）淘选一个大的非免疫抗体库对可溶性形式的HeV附着包膜糖蛋白G（SG（HeV））。这些抗体之一，m102，表现出最高水平的NiV和HeVG的交叉反应性中和，通过轻链改组结合其重链可变结构域的随机诱变和针对sGHeV的淘选来亲和力成熟。所选抗体Fab克隆之一m102.4与sGHeV的结合亲和力等于或高于其他Fab;将其转化为IgG 1并针对感染性NiV和HeV进行测试。它表现出异常有效的和交叉反应的抑制活性，50%抑制浓度分别低于0.04和0.6 μ g/ mL。病毒中和活性与抗体对sG（HeV）和sG（NiV）的结合亲和力相关。m102.4与可溶形式的NiV G（sG（NiV））的结合优于其与sG（HeV）的结合，并且其与HeV的中和优于NiV，尽管最初选择针对sGHeV。这些结果表明，m102.4具有作为治疗剂用于治疗由亨尼帕病毒引起的疾病的潜力。它也可用于预防和诊断，并作为研究试剂。
We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG(HeV)). One of these antibodies, m102, which exhibited the highest level of crossreactive neutralization of both NiV and HeVG, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and crossreactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 mu g/ mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG(HeV) and sG(NiV). m102.4 bound a soluble form of NiV G (sG(NiV)) better than it bound sG(HeV), and it neutralized NiV better than HeV, despite being originally selected against sGHeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent.