中文摘要：单克隆抗体被动免疫将在对抗COVID-19中发挥重要作用。最近出现的病毒变异，对一些现有抗体和疫苗的敏感性降低，突显出广泛交叉反应的重要性。本研究描述了利用噬菌体展示技术和B细胞受体（BCR）序列测定法对住院COVID-19患者的抗体库进行深入挖掘，以分离中和抗体并获得对早期抗体应答的认识。这一全面发现方法产生了一组有效的中和抗体，它们结合包括SARS-CoV-1中保守表位在内的不同病毒表位。非ACE2受体阻断抗体结构测定显示了一个以前未知的结合表位，它不受最近报道的任何主要病毒变异的突变影响，包括B.1.1.7(来自英国)，B.1.351(来自南非)和B.1.1.28(来自巴西)。最后，还通过结合RBD对抗体序列与B细胞受体序列进行结合和中和，描述了一个高度收敛的早期抗体反应。类似的IgM衍生序列出现在这个研究组，也曾出现在先前发表的多个独立研究所描述的患者反应中。
外文摘要：Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.
外文关键词：COVID-19；antibodies；convergence；phage display；SARS-CoV-2 variants
作者：Bullen, G；Galson, JD；Hall, G；Villar, P；Moreels, L；Ledsgaard, L；Mattiuzzo, G；Bentley, EM；Masters, EW；Tang, D；Millett, S；Tongue, D；Brown, R；Diamantopoulos, I；Parthiban, K；Tebbutt, C；Leah, R；Chaitanya, K；Ergueta-Carballo, S；Pazeraitis, D；Surade, SB；Ashiru, O；Crippa, L；Cowan, R；Bowler, MW；Campbell, JI；Lee, WYJ；Carr, MD；Matthews, D；Pfeffer, P；Hufton, SE；Sawmynaden, K；Osbourn, J；John, Karatt-Vellatt, A
作者单位：IONTAS Ltd；Alchemab Therapeut Ltd；Univ Leicester；Natl Inst Biol Stand & Controls；LifeArc；Abcam；European Mol Biol Lab；Queen Mary Univ London
期刊名称：FRONTIERS IN IMMUNOLOGY
期刊影响因子：5.085
出版年份：2021
出版刊次：12
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