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Cell Rep . Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

tetano

Editor, Senior Moderator
Cell Rep


. 2023 Mar 7;42(4):112271.
doi: 10.1016/j.celrep.2023.112271. Online ahead of print.
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses


Aiste Dijokaite-Guraliuc[SUP] 1 [/SUP], Raksha Das[SUP] 1 [/SUP], Daming Zhou[SUP] 2 [/SUP], Helen M Ginn[SUP] 3 [/SUP], Chang Liu[SUP] 4 [/SUP], Helen M E Duyvesteyn[SUP] 5 [/SUP], Jiandong Huo[SUP] 5 [/SUP], Rungtiwa Nutalai[SUP] 1 [/SUP], Piyada Supasa[SUP] 1 [/SUP], Muneeswaran Selvaraj[SUP] 1 [/SUP], Thushan I de Silva[SUP] 6 [/SUP], Megan Plowright[SUP] 6 [/SUP], Thomas A H Newman[SUP] 6 [/SUP], Hailey Hornsby[SUP] 7 [/SUP], Alexander J Mentzer[SUP] 8 [/SUP], Donal Skelly[SUP] 9 [/SUP], Thomas G Ritter[SUP] 10 [/SUP], Nigel Temperton[SUP] 11 [/SUP], Paul Klenerman[SUP] 12 [/SUP], Eleanor Barnes[SUP] 12 [/SUP], Susanna J Dunachie[SUP] 13 [/SUP]; OPTIC consortium; Cornelius Roemer[SUP] 14 [/SUP], Thomas P Peacock[SUP] 15 [/SUP], Neil G Paterson[SUP] 3 [/SUP], Mark A Williams[SUP] 3 [/SUP], David R Hall[SUP] 3 [/SUP], Elizabeth E Fry[SUP] 16 [/SUP], Juthathip Mongkolsapaya[SUP] 17 [/SUP], Jingshan Ren[SUP] 18 [/SUP], David I Stuart[SUP] 19 [/SUP], Gavin R Screaton[SUP] 20 [/SUP]



Collaborators, Affiliations

Abstract

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.

Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2, BA.2, variant, mutation, RBD, antibodies, binding site, breakthrough, neutralizing, structure, COVID-19.
 
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