State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Cell Rep. 2022 May 24;39(8):110862. doi: 10.1016/j.celrep.2022.110862. Epub 2022 May 8.
The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.
奥密克戎变异株高度耐受疫苗、恢复期血清和中和抗体（nAbs），这突显了迫切需要强效治疗性 nAbs。在此，一组来自严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）恢复期患者的人源 nAbs 对奥密克戎表现出不同程度的中和作用，其中 XMA01 和 XMA04 保持纳摩尔亲和力和优异的中和活性（半数最大抑制浓度 [IC50]：约 20ng/mL）。nAb XMA09 对所有关注的变体（VOCs）以及 SARS-CoV 均表现出微弱但未减弱的中和作用。结构分析表明，上述三种抗体可协同结合野生型和奥密克戎刺突的受体结合域（RBD），并定义了 nAb 介导的广泛中和的关键决定因素。三种 nAbs 对奥密克戎具有协同中和作用，这是由于 XMA04 和 XMA01（或 XMA09）之间的抗体间相互作用所致。此外，XMA01/XMA04 鸡尾酒可协同保护仓鼠免受 Beta 和奥密克戎变异株感染。总之，我们的研究结果为针对奥密克戎的抗体鸡尾酒疗法或通用疫苗的合理设计提供了思路。
