小柯机器人

美国哥伦比亚大学何大一、Yaoxing Huang等研究人员合作发现，SARS-CoV-2变体B.1.351和B.1.1.7出现抗体耐药性。2021年3月8日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，COVID-19大流行已席卷全球，其病原体SARS-CoV-2仍在传播。结束这场大流行取决于有效的干预措施。单抗和组合单克隆抗体（mAb）疗法已获得紧急使用授权，更多的策略也正在筹备中。此外，多种疫苗已显示了潜力，其中两种具有约95％的保护功效。但是，这些干预措施是针对于2019年出现的SARS-CoV-2。在英国和南非出现了新的SARS-CoV-2变体B.1.351和B1.2.1。这是令人担忧的，因为它们更易于传播，并且刺突蛋白发生广泛的突变。

研究人员发现，B.1.1.7难以被大多数mAb中和突刺的N末端结构域（NTD），并且相对耐受一些靶向受体结合域（RBD）的mAb。但它对恢复期血浆或疫苗后的血清没有更高的抗性。B.1.351上的发现更令人担忧，因为这种变体不仅难于被大多数NTD mAb所中和，而且难以被RBD上受体结合基序的多个单个mAb所中和，这在很大程度上是由于E484K突变所致。此外，B.1.351对恢复性血浆（9.4倍）和疫苗后血清（10.3-12.4倍）的中和作用具有明显的抗性。 B.1.351和具有相似突刺突变的新兴变体对mAb治疗提出了新的挑战，并威胁到当前疫苗的保护功效。 

附：英文原文

Title: Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

Author: Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho

Issue&Volume: 2021-03-08

Abstract: The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. The prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1–3, with more in the pipeline4–7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of the spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

DOI: 10.1038/s41586-021-03398-2

Source: https://www.nature.com/articles/s41586-021-03398-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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