You Lei, Zhang Luning, Ouyang Shengqun, Gao Bo, Li Yanan, Li Jialu, Wu Ningbo, Wang Hong, Sun Shiqi, Li Jinfeng, Yin Zi, Xu Ziyang, Chen Yao, Zhu Yiwen, Zhang Shuangyan, Xu Zhan, Zhang Tianyu, Liu Zhaoyuan, Huang Chuanxin, Li Bin, Qu Jieming, Su Bing, Yeap Leng-Siew
Shanghai Institute of Immunology and Department of Pulmonary and Critical Care Medicine, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China.
Cell Discov. 2025 May 20;11(1):49. doi: 10.1038/s41421-025-00800-5.
Despite high vaccination rates, highly evolved Omicron variants have caused widespread infections and, in some cases, recurrent infections in the human population. As the population continues to be threatened by new variants, it is critical to understand how the dynamic cross-reactive antibody response evolves and affects protection. Here, we longitudinally profiled neutralizing antibodies in individuals who experienced three Omicron waves in China over an 18-month period following the lifting of the COVID restriction. We found that individuals with BA.5/BF.7 and XBB dual infections had increased breadth and neutralizing potency of Omicron-specific antibodies compared to those with a BA.5/BF.7 single infection, and were thus more resistant to JN.1/XDV.1 infection in the third wave. During the second infection, a new imprint based on the previously infected variant was established, and the antibodies developed high cross-reactivity against the Omicron variants and less against vaccine-derived WT SARS-CoV-2. Our results suggest that the high titer and breadth of cross-reactive antibodies from multiple infections may be protective against future infection with Omicron variants such as JN.1, but may still be vulnerable to antigenically advanced subvariants such as KP.3.1.1 and XEC.
尽管疫苗接种率很高，但高度进化的奥密克戎变种已导致广泛感染，在某些情况下还导致人群反复感染。随着人群继续受到新变种的威胁，了解动态交叉反应抗体反应如何演变以及如何影响保护作用至关重要。在这里，我们对在中国解除新冠疫情限制后的18个月内经历了三轮奥密克戎疫情的个体的中和抗体进行了纵向分析。我们发现，与仅感染BA.5/BF.7的个体相比，同时感染BA.5/BF.7和XBB的个体的奥密克戎特异性抗体的广度和中和效力有所增加，因此在第三波疫情中对JN.1/XDV.1感染更具抵抗力。在第二次感染期间，基于先前感染变种建立了新的印记，并且抗体对奥密克戎变种产生了高交叉反应性，而对疫苗衍生的野生型SARS-CoV-2的交叉反应性较低。我们的结果表明，多次感染产生的高滴度和广泛的交叉反应抗体可能对未来感染奥密克戎变种（如JN.1）具有保护作用，但可能仍然易受抗原性更高级的亚变种（如KP.3.1.1和XEC）的影响。
