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严重急性呼吸综合征冠状病毒2（SARS-CoV-2）亚变体KP.3.1.1和XEC的抗体逃避性

Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC.

作者信息

Wang Qian, Guo Yicheng, Mellis Ian A, Wu Madeline, Mohri Hiroshi, Gherasim Carmen, Valdez Riccardo, Purpura Lawrence J, Yin Michael T, Gordon Aubree, Ho David D

机构信息

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Pandemic Research Alliance Unit at the Wu Center for Pandemic Research, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

出版信息

Cell Rep. 2025 Apr 22;44(4):115543. doi: 10.1016/j.celrep.2025.115543. Epub 2025 Apr 8.

DOI:10.1016/j.celrep.2025.115543
PMID:40202847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12014523/
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread, and it remains critical to understand the functional consequences of mutations in dominant viral variants. The recombinant JN.1 subvariant XEC recently replaced KP.3.1.1 to become the most prevalent subvariant worldwide. Here, we measure the in vitro neutralization of KP.3.1.1 and XEC by human sera, monoclonal antibodies, and the soluble human ACE2 (hACE2) receptor relative to the parental subvariants KP.3 and JN.1. KP.3.1.1 and XEC are slightly more resistant (1.3- to 1.6-fold) than KP.3 to serum neutralization and antigenically similar. Both also demonstrate greater resistance to neutralization by select monoclonal antibodies and soluble hACE2, all of which target the top of the viral spike. Our findings suggest that the upward motion of the receptor-binding domain in the spike may be partially hindered by the N-terminal domain mutations in KP.3.1.1 and XEC, allowing these subvariants to better evade serum antibodies that target the viral spike in the up position and to have a growth advantage.

摘要

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）持续进化和传播，了解主要病毒变体中突变的功能后果仍然至关重要。重组JN.1亚变体XEC最近取代了KP.3.1.1，成为全球最流行的亚变体。在此，我们测定了人血清、单克隆抗体和可溶性人血管紧张素转换酶2（hACE2）受体相对于亲本亚变体KP.3和JN.1对KP.3.1.1和XEC的体外中和作用。KP.3.1.1和XEC对血清中和的抗性比KP.3略高（1.3至1.6倍），且抗原性相似。两者对选定的单克隆抗体和可溶性hACE2的中和作用也表现出更强的抗性，所有这些都靶向病毒刺突的顶部。我们的研究结果表明，刺突中受体结合结构域的向上运动可能部分受到KP.3.1.1和XEC中N端结构域突变的阻碍，使这些亚变体能够更好地逃避靶向向上位置病毒刺突的血清抗体，并具有生长优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/b8103cc81f89/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/9488797d249a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/23f0ccdce6de/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/b8103cc81f89/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/9488797d249a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/23f0ccdce6de/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d9/12014523/b8103cc81f89/gr2.jpg

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引用本文的文献

[1]
Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.

bioRxiv. 2025-8-19

[2]
Multiscale Modeling and Dynamic Mutational Profiling of Binding Energetics and Immune Escape for Class I Antibodies with SARS-CoV-2 Spike Protein: Dissecting Mechanisms of High Resistance to Viral Escape Against Emerging Variants.

Viruses. 2025-7-23

[3]
Age and primary vaccination schedule impact humoral and cellular immunity with an inactivated SARS-CoV-2 vaccine.

iScience. 2025-7-21

[4]
Neutralization Activity of Standard and Hyperimmune Intravenous Immunoglobulins Against Recently Circulating SARS-CoV-2 Variants.

Vaccines (Basel). 2025-7-17

[5]
The XEC Variant: Genomic Evolution, Immune Evasion, and Public Health Implications.

Viruses. 2025-7-15

[6]
Structural and functional insights into the evolution of SARS-CoV-2 KP.3.1.1 spike protein.

Cell Rep. 2025-7-4

[7]
Optimizing a human monoclonal antibody for better neutralization of SARS-CoV-2.

Nat Commun. 2025-7-4

[8]
Discovery of Synergistic Broadly Neutralizing Antibodies Targeting Non-Dominant Epitopes on SARS-CoV-2 RBD and NTD.

Vaccines (Basel). 2025-5-30

[9]
KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2.

Lancet Infect Dis. 2025-3

[10]
Structural and Functional Insights into the Evolution of SARS-CoV-2 KP.3.1.1 Spike Protein.

bioRxiv. 2024-12-10

本文引用的文献

[1]
Role of glycosylation mutations at the N-terminal domain of SARS-CoV-2 XEC variant in immune evasion, cell-cell fusion, and spike stability.

J Virol. 2025-4-15

[2]
KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2.

Lancet Infect Dis. 2025-3

[3]
Antiviral humoral immunity induced by JN.1 monovalent mRNA vaccines against SARS-CoV-2 omicron subvariants including JN.1, KP.3.1.1, and XEC.

Lancet Infect Dis. 2025-2

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Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations.

Lancet Infect Dis. 2025-1

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Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages.

N Engl J Med. 2024-11-14

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Lancet Infect Dis. 2024-12

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Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages.

Emerg Microbes Infect. 2024-12

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Mol Cell. 2024-7-25

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XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1.

Cell Host Microbe. 2024-3-13

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Nature. 2023-12

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