GlobalBio, Inc., 320 Concord Ave, Cambridge, MA 02138, USA.
Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico.
Int J Mol Sci. 2022 Aug 28;23(17):9763. doi: 10.3390/ijms23179763.
Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.
自 2019 年 12 月首次报告 COVID-19 以来，这种由 SARS-CoV-2 引起的病毒感染已导致数百万人死亡。为了控制 COVID-19 大流行，食品和药物管理局（FDA）和/或欧洲药品管理局（EMA）已授予九种治疗性抗体紧急使用授权（EUA）。尽管如此，SARS-CoV-2 的自然进化产生了许多令人关注的变体（VOC），这对 EUA 抗体的疗效提出了挑战。在这里，我们回顾了这些治疗性抗体的最相关特征，包括批准时间、对 VOC 的中和谱、可变区选择方法、体细胞突变、HCDR3 和 LCDR3 特征、同种型、治疗形式中使用的 Fc 修饰以及 SARS-CoV-2 受体结合域（RBD）上的表位识别。审查的结论之一是，仍然对新的 VOC 保留疗效的 EUA 治疗性抗体结合由保守残基形成的表位，这些残基似乎在进化上保守，因此对 RBD：hACE-2 相互作用至关重要。这里审查的信息应该有助于设计新的、更有效的抗体来预防和/或治疗 COVID-19 以及其他传染病。
