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).
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。