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

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.

SUBMITTER: Dijokaite-Guraliuc A

PROVIDER: S-EPMC9988707 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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

Dijokaite-Guraliuc Aiste A Das Raksha R Zhou Daming D Ginn Helen M HM Liu Chang C Duyvesteyn Helen M E HME Huo Jiandong J Nutalai Rungtiwa R Supasa Piyada P Selvaraj Muneeswaran M de Silva Thushan I TI Plowright Megan M Newman Thomas A H TAH Hornsby Hailey H Mentzer Alexander J AJ Skelly Donal D Ritter Thomas G TG Temperton Nigel N Klenerman Paul P Barnes Eleanor E Dunachie Susanna J SJ Roemer Cornelius C Peacock Thomas P TP Paterson Neil G NG Williams Mark A MA Hall David R DR Fry Elizabeth E EE Mongkolsapaya Juthathip J Ren Jingshan J Stuart David I DI Screaton Gavin R GR

Cell reports 20230307 4

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 sub ...[more]

PMID: 36995936

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Project description:The first dominant SARS-CoV-2 Omicron variant BA.1 harbours 35 mutations in its Spike protein from the original SARS-CoV-2 variant that emerged late 2019. Soon after its discovery, BA.1 rapidly emerged to become the dominant variant worldwide and has since evolved into several variants. Omicron is of major public health concern owing to its high infectivity and antibody evasion. This review article examines the theories that have been proposed on the evolution of Omicron including zoonotic spillage, infection in immunocompromised individuals and cryptic spread in the community without being diagnosed. Added to the complexity of Omicron's evolution are the multiple reports of recombination events occurring between co-circulating variants of Omicron with Delta and other variants such as XE. Current literature suggests that the combination of the novel mutations in Omicron has resulted in the variant having higher infectivity than the original Wuhan-Hu-1 and Delta variant. However, severity is believed to be less owing to the reduced syncytia formation and lower multiplication in the human lung tissue. Perhaps most challenging is that several studies indicate that the efficacy of the available vaccines have been reduced against Omicron variant (8-127 times reduction) as compared to the Wuhan-Hu-1 variant. The administration of booster vaccine, however, compensates with the reduction and improves the efficacy by 12-35 fold. Concerningly though, the broadly neutralising monoclonal antibodies, including those approved by FDA for therapeutic use against previous SARS-CoV-2 variants, are mostly ineffective against Omicron with the exception of Sotrovimab and recent reports suggest that the Omicron BA.2 is also resistant to Sotrovimab. Currently two new Omicron variants BA.4 and BA.5 are emerging and are reported to be more transmissible and resistant to immunity generated by previous variants including Omicron BA.1 and most monoclonal antibodies. As new variants of SARS-CoV-2 will likely continue to emerge it is important that the evolution, and biological consequences of new mutations, in existing variants be well understood.

Dataset Information

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

Publications

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

Similar Datasets

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