A cross-protective mAb recognizes a novel epitope within the flavivirus NS1 protein
A cross-protective mAb recognizes a novel epitope within the flavivirus NS1 protein
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DOI：
10.1099/vir.0.036640-0
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发表时间：
2012-01-01
影响因子：
3.8
通讯作者：
Chung, Kyung Min
中科院分区：
文献类型：
--
作者：
Lee, Tae Hee;Song, Byung-Hak;Chung, Kyung Min
尽管黄病毒感染在世界范围内死灰复燃，但对于该属的任何成员都不存在批准的治疗剂。虽然已经产生了具有抗黄病毒治疗潜力的交叉反应性抗体，但它们中的大多数是具有引起黄病毒感染和疾病的抗体依赖性增强的潜力的抗E抗体。我们先前描述了针对西尼罗河病毒（WNV）的非结构性NS 1蛋白的mAb，当在WNV感染前或感染后给药时，所述mAb在小鼠中具有保护性。在这里，我们证明了这些单克隆抗体（16 NS 1）与日本脑炎病毒（JEV）的交叉反应，并表现出对致命的JEV感染的保护活性。结合位点特异性突变的重叠肽图谱分析鉴定了16 NS 1 mAb结合的新表位（116）KAWGKSILFA（125）和关键氨基酸残基（118）W和（122）I。这些结果可能有助于开发一种广泛治疗的mAb，该mAb缺乏增强潜力和/或针对靶向NS 1蛋白的黄病毒的基于亚基的疫苗。
Despite a resurgence of flavivirus infections worldwide, no approved therapeutic agent exists for any member of the genus. While cross-reactive antibodies with therapeutic potential against flaviviruses have been generated, the majority of them are anti-E antibodies with the potential to cause antibody-dependent enhancement of flavivirus infection and disease. We described previously mAbs against the non-structural NS1 protein of the West Nile virus (WNV) that were protective in mice when administered pre- or post-infection of WNV. Here, we demonstrate that one of these mAbs (16NS1) cross-reacted with Japanese encephalitis virus (JEV) and exhibited protective activity against a lethal JEV infection. Overlapping peptide mapping analysis combined with site-specific mutations identified a novel epitope (116)KAWGKSILFA(125) and critical amino acid residues ((118)W and (122)I) for 16NS1 mAb binding. These results may facilitate the development of a broadly therapeutic mAb that lacks enhancing potential and/or subunit-based vaccine against flaviviruses that target the NS1 protein.