Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual.

Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual.
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DOI:
10.1016/j.isci.2023.108009
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发表时间:
2023-10-20
期刊:
影响因子:
5.8
通讯作者:
van Gils, Marit J.
van Gils, Marit J.
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Guerra, Denise;Beaumont, Tim;Radic, Laura;Kerster, Gius;van der Straten, Karlijn;Yuan, Meng;Torres, Jonathan L.;Lee, Wen-Hsin;Liu, Hejun;Poniman, Meliawati;Bontjer, Ilja;Burger, Judith A.;Claireaux, Mathieu;Caniels, Tom G.;Snitselaar, Jonne L.;Bijl, Tom P. L.;Kruijer, Sabine;Ozorowski, Gabriel;Gideonse, David;Sliepen, Kwinten;Ward, Andrew B.;Eggink, Dirk;de Bree, Godelieve J.;Wilson, Ian A.;Sanders, Rogier W.;van Gils, Marit J.

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由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的大流行仍然是一个医学威胁,因为对疫苗和先前感染产生抗药性的多种变种的进化。因此,发现能中和多种SARS-CoV-2变异株的单抗势在必行。一种稳定的尖峰糖蛋白被用来从一名原发伽玛变异型感染者身上浓缩抗原特异性B细胞。从这些B细胞中筛选出的5株单抗对多种变异体显示出相当强的中和能力,其中COVA309-35对自体病毒的中和活性最强,Omicron BA.1和BA.2以及COVA309-22对Omicron BA.4/5、BQ.1.1和XBB.1具有结合和中和活性。当将COVA309单抗作为鸡尾酒或双特异性抗体结合时,其广度和效价都得到了提高。此外,通过结构分析,阐明了COVA309单抗的交叉中和机理。总而言之,这些数据表明,伽玛病毒感染者可以产生广泛的中和抗体。初次感染SARS-CoV-2伽玛变种引起有效和广泛的抗体COVA309抗体结合和中和广泛的SARS-CoV-2变种双特异性Cova抗体显示中和广度增加免疫学;病毒学;结构生物学
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has remained a medical threat due to the evolution of multiple variants that acquire resistance to vaccines and prior infection. Therefore, it is imperative to discover monoclonal antibodies (mAbs) that neutralize a broad range of SARS-CoV-2 variants. A stabilized spike glycoprotein was used to enrich antigen-specific B cells from an individual with a primary Gamma variant infection. Five mAbs selected from those B cells showed considerable neutralizing potency against multiple variants, with COVA309-35 being the most potent against the autologous virus, as well as Omicron BA.1 and BA.2, and COVA309-22 having binding and neutralization activity against Omicron BA.4/5, BQ.1.1, and XBB.1. When combining the COVA309 mAbs as cocktails or bispecific antibodies, the breadth and potency were improved. In addition, the mechanism of cross-neutralization of the COVA309 mAbs was elucidated by structural analysis. Altogether these data indicate that a Gamma-infected individual can develop broadly neutralizing antibodies. Primary infection with the SARS-CoV-2 Gamma variant elicits potent and broad antibodies COVA309 antibodies bind and neutralize a wide range of SARS-CoV-2 variants Bispecific COVA antibodies show increased neutralization breadth Immunology; Virology; Structural biology
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