Zhou Panpan, Song Ge, He Wan-Ting, Beutler Nathan, Tse Longping V, Martinez David R, Schäfer Alexandra, Anzanello Fabio, Yong Peter, Peng Linghang, Dueker Katharina, Musharrafieh Rami, Callaghan Sean, Capozzola Tazio, Yuan Meng, Liu Hejun, Limbo Oliver, Parren Mara, Garcia Elijah, Rawlings Stephen A, Smith Davey M, Nemazee David, Jardine Joseph G, Wilson Ian A, Safonova Yana, Rogers Thomas F, Baric Ralph S, Gralinski Lisa E, Burton Dennis R, Andrabi Raiees
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
bioRxiv. 2022 Mar 7:2022.03.04.479488. doi: 10.1101/2022.03.04.479488.
Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against coronaviruses that cause severe disease, for anticipating novel pandemic-causing viruses, and to respond more effectively to SARS-CoV-2 variants. The emergence of the Omicron variant of SARS-CoV-2 has illustrated the limitations of solely targeting the receptor binding domain (RBD) of the envelope Spike (S)-protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors that target a conserved S2 region in the fusion machinery on betacoronavirus spikes. Select bnAbs show broad protection against all three pathogenic betacoronaviruses, SARS-CoV-1, SARS-CoV-2 and MERS-CoV, that have spilled over into humans in the past 20 years to cause severe disease. The bnAbs provide new opportunities for antibody-based interventions and key insights for developing pan-betacoronavirus vaccines.
泛β冠状病毒中和抗体可能是开发针对导致严重疾病的冠状病毒的广泛保护性疫苗、预测新型大流行病毒以及更有效应对SARS-CoV-2变体的关键。SARS-CoV-2奥密克戎变体的出现说明了仅靶向包膜刺突（S）蛋白的受体结合域（RBD）的局限性。在这里，我们从接种过SARS-CoV-2康复疫苗的供体中分离出大量广泛中和抗体（bnAbs），这些抗体靶向β冠状病毒刺突融合机制中的一个保守S2区域。选定的bnAbs对过去20年中传播给人类并导致严重疾病的三种致病性β冠状病毒SARS-CoV-1、SARS-CoV-2和MERS-CoV均显示出广泛的保护作用。这些bnAbs为基于抗体的干预措施提供了新机会，并为开发泛β冠状病毒疫苗提供了关键见解。
