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Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

<div class='caption-title'>Identification of high-confidence clonotypes by single-cell transcriptomic and BCR profiling.</div>
<div class='caption-title'>Discovery and characterization of isolated neutralizing antibodies.</div>
<div class='caption-title'>Evaluation of elite antibodies against Omicron BA.2.12.1 and BA.4 & 5.</div>
Guo Y, Zhang G, Yang Q, Xie X, Lu Y, Cheng X, Wang H, Liang J, Tang J, Gao Y, Shang H, Dai J, Shi Y, Zhou J, Zhou J, Guo H, Yang H, Qi J, Liu L, Ma S, Zhang B, Huo Q, Xie Y, Wu J, Dong F, Zhang S, Lou Z, Gao Y, Song Z, Wang W, Sun Z, Yang X, Xiong D, Liu F, Chen X, Zhu P, Wang X, Cheng T, Rao Z
OpenAccess logo Nat Commun 14 3537 (2023)
Related entries: 7yve, 7yvf, 7yvg, 7yvh, 7yvi, 7yvj, 7yvk, 7yvl, 7yvm, 7yvo, 7yvp, 8gou, 8gpy

Cited: 5 times
EuropePMC logo PMID: 37322000

Abstract

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Reviews citing this publication (1)

  1. Single-cell sequencing to multi-omics: technologies and applications. Wu X, Yang X, Dai Y, Zhao Z, Zhu J, Guo H, Yang R. Biomark Res 12 110 (2024)

Articles citing this publication (4)

  1. Fast-Track Discovery of SARS-CoV-2-Neutralizing Antibodies from Human B Cells by Direct Functional Screening. Hillenbrand M, Esslinger C, Seidenberg J, Weber M, Zingg A, Townsend C, Eicher B, Rutkauskaite J, Riese P, Guzman CA, Fischer K, Schmitt S. Viruses 16 339 (2024)
  2. Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents. Yan Q, Zhang Y, Hou R, Pan W, Liang H, Gao X, Deng W, Huang X, Qu L, Tang C, He P, Liu B, Wang Q, Zhao X, Lin Z, Chen Z, Li P, Han J, Xiong X, Zhao J, Li S, Niu X, Chen L. Emerg Microbes Infect 13 2290841 (2024)
  3. Molecular mechanism and structure-guided humanization of a broadly neutralizing antibody against SFTSV. Yang P, Wu X, Shang H, Sun Z, Wang Z, Song Z, Yuan H, Deng F, Shen S, Guo Y, Zhang N. PLoS Pathog 20 e1012550 (2024)
  4. Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation. Chen Y, Zha J, Xu S, Shao J, Liu X, Li D, Zhang X. Viruses 16 566 (2024)


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