美国犹他大学Tyler N. Starr等研究人员合作发现一种对表位多样化具有抗性的广谱沙贝病毒中和抗体。2024年10月8日，《细胞》杂志在线发表了这项成果。
研究人员表示，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的演变导致病毒逃避了临床批准的单克隆抗体（mAb），因此迫切需要对表位多样化具有抗性的mAb。尽管进行了广泛研究，但能够满足临床开发需求并在病毒演化过程中保持活性的广谱中和冠状病毒mAb仍未被广泛发现。
研究人员鉴定出一种名为VIR-7229的人源mAb，它靶向病毒的受体结合基序（RBM），具有前所未有的跨所有沙贝病毒类群的交叉反应性，包括不使用ACE2的蝙蝠沙贝病毒，并且自2019年以来，能够强效中和SARS-CoV-2的变异株，包括最近的EG.5、BA.2.86和JN.1。VIR-7229能容忍极端的表位变异，这部分归因于其高结合亲和力、受体分子模拟及与RBM骨架原子的相互作用。
因此，VIR-7229对逃逸突变的选择具有高度屏障，而这些突变极为罕见且伴随着病毒适应性的下降，这突显了其在未来病毒演化中的潜在抗性。VIR-7229是一种有望成为下一代药物的强效候选者。
附：英文原文
Title: A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification
Author: Laura E. Rosen, M. Alejandra Tortorici, Anna De Marco, Dora Pinto, William B. Foreman, Ashley L. Taylor, Young-Jun Park, Dana Bohan, Tyson Rietz, John M. Errico, Kevin Hauser, Ha V. Dang, Justin W. Chartron, Martina Giurdanella, Giuseppe Cusumano, Christian Saliba, Fabrizia Zatta, Kaitlin R. Sprouse, Amin Addetia, Samantha K. Zepeda, Jack Brown, Jimin Lee, Exequiel Dellota, Anushka Rajesh, Julia Noack, Qiqing Tao, Yvonne DaCosta, Brian Tsu, Rima Acosta, Sambhavi Subramanian, Guilherme Dias de Melo, Lauriane Kergoat, Ivy Zhang, Zhuoming Liu, Barbara Guarino, Michael A. Schmid, Gretja Schnell, Jessica L. Miller, Florian A. Lempp, Nadine Czudnochowski, Elisabetta Cameroni, Sean P.J. Whelan, Hervé Bourhy, Lisa A. Purcell, Fabio Benigni, Julia di Iulio, Matteo Samuele Pizzuto, Antonio Lanzavecchia, Amalio Telenti, Gyorgy Snell, Davide Corti, David Veesler, Tyler N. Starr
Issue&Volume: 2024-10-08
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.
DOI: 10.1016/j.cell.2024.09.026
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01084-5