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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Immunity. 2023 Mar 14;56(3):669-686.e7. doi: 10.1016/j.immuni.2023.02.005. Epub 2023 Feb 16.
Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.
针对新型大流行冠状病毒开发广泛保护疫苗以及更有效地应对 SARS-CoV-2 变体的关键可能在于泛β冠状病毒中和抗体。Omicron 和 SARS-CoV-2 的亚变体的出现说明了仅针对刺突（S）蛋白受体结合域（RBD）的局限性。在这里，我们从 SARS-CoV-2 康复接种供体中分离出了一大类广泛中和抗体（bnAb），这些抗体针对β冠状病毒刺突融合机制中的保守 S2 区域。一些选择的 bnAb 显示出对过去 20 年中在人类中溢出的三种致命β冠状病毒（SARS-CoV-1、SARS-CoV-2 和 MERS-CoV）的广泛体内保护作用。对这些 bnAb 的结构研究描绘了它们广泛反应性的分子基础，并揭示了可通过广泛疫苗接种策略靶向的常见抗体特征。这些 bnAb 为基于抗体的干预措施和开发泛β冠状病毒疫苗提供了新的见解和机会。
