Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-05-10 Epub Date: 2024-04-03 DOI:10.1016/j.medj.2024.03.006

Qingwen He, Yaling An, Xuemei Zhou, Haitang Xie, Lifeng Tao, Dedong Li, Anqi Zheng, Linjie Li, Zepeng Xu, Shufan Yu, Ruyue Wang, Hua Hu, Kefang Liu, Qihui Wang, Lianpan Dai, Kun Xu, George F Gao

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Abstract

Background: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1.

Methods: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes.

Findings: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape.

Conclusions: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines.

Funding: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).

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二聚受体结合域亚基疫苗抗血清和 41 种人类单克隆抗体对 EG.5、EG.5.1、BA.2.86 和 JN.1 的中和作用。

背景：与BA.2或XBB.1.5相比，最近发现的循环型奥米克龙变体BA.2.86和JN.1在尖峰蛋白上有超过30个氨基酸的变化。本研究旨在全面评估 BA.2.86、JN.1、EG.5 和 EG.5.1 的免疫逃逸潜力：我们收集了人类和小鼠血清，以评估血清学中和活性。参与者接种了三剂冠状病毒病2019（COVID-19）疫苗或一剂加强剂量的ZF2022-A疫苗（Delta-BA.5受体结合域[RBD]-heterodimer免疫原），或经历了一次突破性感染（BTI）。ZF2202-A 疫苗正在进行临床试验研究（ClinicalTrials.gov：NCT05850507）。BALB/c 小鼠接种了一组严重急性呼吸道综合征冠状病毒 2 RBD 二聚体蛋白。用 41 种针对 8 个 RBD 表位的代表性人类单克隆抗体分析了这些变体的抗体逃避特性：我们发现，BA.2.86 的中和逃避能力低于 EG.5 和 EG.5.1。ZF2202-A 增强剂诱导的中和滴度明显高于 BTI。此外，在RBD-4和RBD-5表位上，BA.2.86和JN.1比EG.5和EG.5.1表现出更强的抗体逃避能力。与 BA.2.86 相比，JN.1 进一步丧失了与几种 RBD-1 单克隆抗体结合的能力，并表现出进一步的免疫逃避：我们的数据显示，与 BA.2.86 和 EG.5.1 相比，目前占主导地位的亚变体 JN.1 显示出更强的免疫逃避能力，这一点非常值得关注。这项研究及时对相关亚变体进行了风险评估，并为更新 COVID-19 疫苗提供了依据：本研究得到了国家重点研发计划、国家自然科学基金、北京生命科学研究院、比尔及梅琳达-盖茨基金会和中国博士后科学基金会博士后基金项目的资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.