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.
RESULTS: 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.
BACKGROUND: 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).
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.
RESULTS: 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.
BACKGROUND: 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).
摘要：
背景：与BA.2或XBB.1.5相比，最近流行的Omicron变体BA.2.86和JN.1在刺突蛋白上有30多个氨基酸变化。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。
方法：我们收集了人和鼠血清以评估血清学中和活性。参与者接受了三剂2019冠状病毒病（COVID-19）疫苗或加强剂量的ZF2022-A疫苗（Delta-BA.5受体结合域[RBD]-异二聚体免疫原）或经历了突破性感染（BTI）。ZF2202-A疫苗正在进行临床试验研究（ClinicalTrials.gov：NCT05850507）。BALB/c小鼠接种一组严重急性呼吸综合征冠状病毒2RBD-二聚体蛋白。用靶向8个RBD表位的41种代表性人单克隆抗体分析这些变体的抗体逃避性质。
结果：我们发现，在人类中，BA.2.86比EG.5和EG.5.1具有更少的中和逃避。ZF2202-A加强剂诱导的中和滴度显著高于BTI。此外，BA.2.86和JN.1在RBD-4和RBD-5表位上表现出比EG.5和EG.5.1更强的抗体逃避。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,并显示出进一步的免疫逃逸。
结论：我们的数据显示，目前占主导地位的亚变体，与BA.2.86和EG.5.1相比，JN.1显示出增强的免疫逃避，这是高度关注的。这项研究为感兴趣的亚变体提供了及时的风险评估，并为更新COVID-19疫苗提供了基础。
背景：这项工作由中国国家重点研发计划资助，国家自然科学基金,北京生命科学研究院,比尔和梅林达·盖茨基金会,和中国博士后科学基金会（CPSF）博士后奖学金计划。
方法：我们收集了人和鼠血清以评估血清学中和活性。参与者接受了三剂2019冠状病毒病（COVID-19）疫苗或加强剂量的ZF2022-A疫苗（Delta-BA.5受体结合域[RBD]-异二聚体免疫原）或经历了突破性感染（BTI）。ZF2202-A疫苗正在进行临床试验研究（ClinicalTrials.gov：NCT05850507）。BALB/c小鼠接种一组严重急性呼吸综合征冠状病毒2RBD-二聚体蛋白。用靶向8个RBD表位的41种代表性人单克隆抗体分析这些变体的抗体逃避性质。
结果：我们发现，在人类中，BA.2.86比EG.5和EG.5.1具有更少的中和逃避。ZF2202-A加强剂诱导的中和滴度显著高于BTI。此外，BA.2.86和JN.1在RBD-4和RBD-5表位上表现出比EG.5和EG.5.1更强的抗体逃避。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,并显示出进一步的免疫逃逸。
结论：我们的数据显示，目前占主导地位的亚变体，与BA.2.86和EG.5.1相比，JN.1显示出增强的免疫逃避，这是高度关注的。这项研究为感兴趣的亚变体提供了及时的风险评估，并为更新COVID-19疫苗提供了基础。
背景：这项工作由中国国家重点研发计划资助，国家自然科学基金,北京生命科学研究院,比尔和梅林达·盖茨基金会,和中国博士后科学基金会（CPSF）博士后奖学金计划。
