SARS-CoV-2 JN.1 变体对 IGHV3-53/3-66 B 细胞种系的规避。

IF 17.6 1区 医学 Q1 IMMUNOLOGY
Ida Paciello, Giuseppe Maccari, Giulio Pierleoni, Federica Perrone, Giulia Realini, Marco Troisi, Gabriele Anichini, Maria Grazia Cusi, Rino Rappuoli, Emanuele Andreano
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引用次数: 0

摘要

严重急性呼吸系统综合征冠状病毒2变异株JN.1与祖先的BA.2.86相比,尽管在尖峰(S)蛋白受体结合域(RBD)上只有一个氨基酸的变化,但最近却成为了主要变异株,而祖先的BA.2.86在全球变异株中的比例从未超过5%。为了在分子水平上确定 JN.1 的全球传播能力,我们对 899 种中和人类单克隆抗体进行了研究。我们的数据显示,JN.1尖峰蛋白RBD中的单个亮氨酸-455-丝氨酸突变释放了JN.1的全球传播能力,这可能是通过消除70%以上由IGHV3-53/3-66种系介导的中和抗体而发生的。然而,中和效力低但 Fc 功能强的第 3 类抗体的恢复力可能是 JN.1 没有出现严重疾病的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines

SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines
The severe acute respiratory syndrome coronavirus 2 variant JN.1 recently emerged as the dominant variant despite having only one amino acid change on the spike (S) protein receptor binding domain (RBD) compared with the ancestral BA.2.86, which never represented more than 5% of global variants. To define at the molecular level the JN.1 ability to spread globally, we interrogated a panel of 899 neutralizing human monoclonal antibodies. Our data show that the single leucine-455–to–serine mutation in the JN.1 spike protein RBD unleashed the global spread of JN.1, likely occurring by elimination of more than 70% of the neutralizing antibodies mediated by IGHV3-53/3-66 germlines. However, the resilience of class 3 antibodies with low neutralization potency but strong Fc functions may explain the absence of JN.1 severe disease.
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来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
期刊介绍: Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.
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