Genomics Public Health Analysis, UK Health Security Agency, London, UK.
Centre for Global Infectious Disease Analysis, Imperial College London, London, England.
Nat Commun. 2023 Jun 7;14(1):3334. doi: 10.1038/s41467-023-37826-w.
COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.
COVID-19 患者可能会接受中和单克隆抗体（mAbs）治疗。为了最大限度地减少病毒逃避中和作用，这些抗体被组合使用，例如 casirivimab+imdevimab，或者对于针对相对保守区域的抗体，单独使用，例如 sotrovimab。英国对 SARS-CoV-2 的前所未有的基因组监测使我们能够采用基于基因组的方法，检测接受 casirivimab+imdevimab 和 sotrovimab 治疗的 Delta 和 Omicron 病例中出现的药物耐药性。突变发生在抗体表位内，对于 casirivimab+imdevimab，多个突变同时存在于连续的原始读数上，同时影响两个成分。我们使用表面等离子体共振和假病毒中和测定法证明这些突变降低或完全消除了抗体亲和力和中和活性，表明它们是由免疫逃逸驱动的。此外，我们还表明，一些突变也降低了疫苗诱导的血清的中和活性。
