Nanoscopic Assessment of Anti-SARS-CoV-2 Spike Neutralizing Antibody Using High-Speed AFM.
Nanoscopic Assessment of Anti-SARS-CoV-2 Spike Neutralizing Antibody Using High-Speed AFM.
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DOI：
10.1021/acs.nanolett.2c04270
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发表时间：
2023-01-25
期刊：
影响因子：
10.8
通讯作者：
Wong, Richard W.
中科院分区：
文献类型：
--
作者：
Lim, Keesiang;Nishide, Goro;Sajidah, Elma Sakinatus;Yamano, Tomoyoshi;Qiu, Yujia;Yoshida, Takeshi;Kobayashi, Akiko;Hazawa, Masaharu;Ando, Toshio;Hanayama, Rikinari;Wong, Richard W.
关键词：
抗刺突中和抗体（S NAb）已被开发用于预防和治疗COVID-19。刺突蛋白和S NAbs之间的动态相互作用的纳米级表征仍然困难。利用高速原子力显微镜（HS-AFM）研究了S NAb的分子特性及其与刺突蛋白的相互作用。S NAb在低密度下表现为Y构象的单体，在高密度下形成六聚体寡聚体。在RBD处的动态S NAb-刺突蛋白相互作用既不诱导RBD打开也不诱导S1亚基脱落。此外，相互作用是稳定的内体pH值。这些结果表明，S NAb可以有一个抗体依赖性增强的风险可以忽略不计。刺突蛋白在小细胞外囊泡（S sEV）上的动态运动与SARS-CoV-2相似。利用HS-AFM可以评估变异的S sEV对S NAb的敏感性。总之，我们展示了一个纳米级的评估平台，用于评估S NAbs的结合性能。
Anti-spike neutralizing antibodies (S NAbs) have been developed for prevention and treatment against COVID-19. The nanoscopic characterization of the dynamic interaction between spike proteins and S NAbs remains difficult. By using high-speed atomic force microscopy (HS-AFM), we elucidate the molecular property of an S NAb and its interaction with spike proteins. The S NAb appeared as monomers with a Y conformation at low density and formed hexameric oligomers at high density. The dynamic S NAb–spike protein interaction at RBD induces neither RBD opening nor S1 subunit shedding. Furthermore, the interaction was stable at endosomal pH. These findings indicated that the S NAb could have a negligible risk of antibody-dependent enhancement. Dynamic movement of spike proteins on small extracellular vesicles (S sEV) resembled that on SARS-CoV-2. The sensitivity of variant S sEVs to S NAb could be evaluated using HS-AFM. Altogether, we demonstrate a nanoscopic assessment platform for evaluating the binding property of S NAbs.
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