小柯机器人

英国牛津大学Gavin R. Screaton等研究人员发现SARS-CoV-2 P.1突变株具有抗体逃逸能力。2021年3月30日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员表示，结束SARS-CoV-2的大流行依赖于疫苗接种。当前的疫苗引发对早期分离株病毒刺突的中和抗体应答。但是，目前出现了具有多个突变的新毒株：来自巴西的P.1，来自南非的B.1.351和来自英国的B.1.1.7（突刺的变化分别为12、10和9个）。

所有这些都在ACE2结合位点发生突变，其中P.1和B.1.351具有几乎相同的三联体：E484K，K417N/T和N501Y，研究人员证明它们对ACE2具有相似的的亲和力增加。研究人员发现，P.1对自然获得的或疫苗诱导的抗体应答的耐药性明显低于B.1.351，这表明RBD之外的变化会影响中和作用。

尽管与两个ACE2结合位点突变相互作用，单克隆抗体222仍能中和所有这三个变异体，研究人员通过结构分析解释了这一点，并使用222轻链在很大程度上恢复了对一类主要抗体的中和能力。 

附：英文原文

Title: Antibody evasion by the P.1 strain of SARS-CoV-2

Author: Wanwisa Dejnirattisai, Daming Zhou, Piyada Supasa, Chang Liu, Alexander J. Mentzer, Helen M. Ginn, Yuguang Zhao, Helen M.E. Duyvesteyn, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Guido C. Paesen, César López-Camacho, Jose Slon-Campos, Thomas S. Walter, Donal Skelly, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola C. Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Christina Dold, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Derrick Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-Rammerstorfer, Sarah Gilbert, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Neil G. Paterson, Mark A. Williams, David R. Hall, Ruben J.G. Hulswit, Thomas A. Bowden, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton

Issue&Volume: 2021-03-30

Abstract: Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

DOI: 10.1016/j.cell.2021.03.055

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00428-1