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Peer reviewedOpen accessSARSCOVID-19

Deep mutational scanning reveals the antibody escape and infectivity landscape of SARS-CoV-2 Omicron JN.1 and XEC receptor-binding domains

Emerging Microbes & Infections·

Chengwei Shao, Lisa Yang, Chuyao Xiao, Yumei Huang, Xiangxi Wang, Ling Chen, Pan Liu, Si Chen, Mingwei Wei, Siyue Jia, Lunbiao Cui, Yiyue Ge, Ming Xu, Xiaoyan Jia, Jingxin Li

DOI
10.1080/22221751.2026.2686472
PMID
42324717
PMCID
PMC13288909
OpenAlex
Study type
Journal article
Publisher
Informa UK Limited
Article type
journal-article
Integrity
current

Why this research matters now

The authors describe the results as relevant to understanding immune escape and fitness in JN.1 and XEC and to evaluating emerging variants, vaccine-strain selection, and therapeutic-antibody development. These implications are based on the reported pseudovirus analysis and are not evidence of a current population-level surveillance signal.

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Structured evidence summary

Research question

The study examined how single amino acid substitutions in the SARS-CoV-2 Omicron JN.1 and XEC receptor-binding domains affect pseudovirus infectivity and antibody escape.

Study design

This was a two-step, non-replicating pseudovirus deep mutational scanning study using full-length spike proteins. Six receptor-binding-domain monoclonal antibodies were screened, and escape mapping was conducted with the two antibodies that retained substantial neutralizing activity against the tested pseudoviruses.

Population and setting

The analysis focused on Omicron JN.1 and its descendant lineage XEC, using pseudoviruses carrying full-length spike backgrounds and systematic single-substitution changes in the receptor-binding domain. Antibody profiling involved six receptor-binding-domain monoclonal antibodies, with two used for subsequent escape mapping.

Main findings

Most tested single receptor-binding-domain substitutions did not substantially increase pseudovirus cellular invasion. Functionally retaining substitutions associated with marked escape from either tested antibody were concentrated mainly in the receptor-binding motif and receptor-binding ridge, and the two antibodies showed different escape-site patterns.

Public-health relevance

The authors describe the results as relevant to understanding immune escape and fitness in JN.1 and XEC and to evaluating emerging variants, vaccine-strain selection, and therapeutic-antibody development. These implications are based on the reported pseudovirus analysis and are not evidence of a current population-level surveillance signal.

Important limitations

The supplied abstract does not provide a dedicated limitations statement. The evidence is based on a non-replicating pseudovirus system, single amino acid substitutions, and escape mapping with two selected antibodies, so the summary is limited to the supplied single-article abstract and metadata and requires the original paper for decision-grade interpretation.

GIDS interpretation

This article is discoverable in the supplied record under SARS/COVID-19 and treatment/vaccination-related topics. It provides laboratory context on antibody escape and pseudovirus infectivity for JN.1 and XEC, but the supplied evidence does not connect it to a live surveillance signal.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

03

Evidence relationships

This article has 10 auditable classifier relationships to diseases, places, topics, and study design.

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