a State Key Lab of Respiratory Disease , the First Affiliated Hospital of Guangzhou Medical University , Guangzhou , People's Republic of China.
b Guangzhou 8th People's Hospital of Guangzhou Medical University , Guangzhou , People's Republic of China.
Emerg Microbes Infect. 2019;8(1):749-759. doi: 10.1080/22221751.2019.1614885.
The Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection.
寨卡病毒（ZIKV）的爆发及其与小头症的关联引发了公众健康关注。为了研究感染 ZIKV 的患者的抗体反应，我们使用单细胞 PCR 从 ZIKV 感染患者的记忆 B 细胞中分离出的包膜（E）蛋白，克隆了 31 种重链和轻链配对的单克隆抗体（mAb）。选择了 3 种对非洲、亚洲和美洲株具有最强和最广泛中和活性的 mAb（7B3、1C11 和 6A6）进行进一步分析。mAb 7B3 对循环美洲株 GZ02 的 IC50 值为 11.6ng/ml。表位作图显示，mAbs 7B3 和 1C11 靶向 EDIII 结构域侧脊（LR）表位的残基 K394，但 7B3 具有更广泛的 LR 表位足迹，并且还识别残基 T335、G337、E370 和 N371。mAb 6A6 识别 EDII 结构域的残基 D67、K118 和 K251。有趣的是，尽管该患者对 DENV 感染呈血清阴性，但源自 VH3-23 和 VK1-5 胚系对的 mAb 1C11 中和了 ZIKV 和 DENV1。mAbs 7B3、1C11 和 6A6 的给药可保护感染致死剂量 ZIKV 的新生 SCID 小鼠。这项研究提供了潜在的治疗性抗体候选物，并深入了解 ZIKV 感染后的抗体反应。
