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针对原始 SARS-CoV-2 刺突蛋白产生的纳米抗体库仍然对快速进化的病毒有效。

Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus.

机构信息

Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States.

出版信息

Elife. 2024 May 7;12:RP89423. doi: 10.7554/eLife.89423.

DOI:10.7554/eLife.89423
PMID:38712823
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11076045/
Abstract

To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single-domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here, we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast et al., 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.

摘要

迄今为止，所有针对 SARS-CoV-2 的主要单克隆抗体治疗模式对最新流行变异体的疗效都显著下降。由于 SARS-CoV-2 的奥密克戎亚谱系占 COVID-19 感染的 90%以上，疫苗接种或先前变异体暴露产生的免疫反应的逃逸构成了重大挑战。针对 SARS-CoV-2 的一种引人注目的新治疗策略是单域抗体，称为纳米抗体，它解决了单克隆抗体的某些局限性。在这里，我们证明了我们针对野生型 SARS-CoV-2 刺突蛋白（Mast 等人，2021 年）产生的高亲和力纳米抗体库仍然对包括奥密克戎 BA.4/BA.5 在内的关注变体有效；有一部分预测可以抵抗新兴 XBB 和 BQ.1.1 亚谱系中的耐药性。此外，我们揭示了纳米抗体鸡尾酒在中和新兴变体方面的协同潜力。我们的研究强调了纳米抗体技术作为一种多功能治疗和诊断工具的强大功能，可用于对抗 SARS-CoV-2 等快速演变的传染病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5d44b2f13dfe/elife-89423-fig7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5e0412f2ed58/elife-89423-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5d44b2f13dfe/elife-89423-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5b99795398e5/elife-89423-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/dc428424a2fe/elife-89423-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/bb70c1a5a5bb/elife-89423-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/a32411a5e453/elife-89423-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/49fbd95d6a25/elife-89423-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/20059f6029ac/elife-89423-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5e0412f2ed58/elife-89423-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb49/11076045/5d44b2f13dfe/elife-89423-fig7.jpg

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A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.一种假病毒系统可实现对完整 SARS-CoV-2 刺突蛋白的深度突变扫描。
Cell. 2023 Mar 16;186(6):1263-1278.e20. doi: 10.1016/j.cell.2023.02.001. Epub 2023 Feb 13.
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Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge.
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Int J Mol Sci. 2023 Jan 23;24(3):2264. doi: 10.3390/ijms24032264.
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