Department of Cell Biology of National Translational Science Center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China.
Signal Transduct Target Ther. 2023 Jan 21;8(1):42. doi: 10.1038/s41392-022-01265-8.
The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.
新冠病毒（SARS-CoV-2）的奥密克戎变体于 2021 年 11 月在南非首次被确认，引发了全球第五波大流行。在此，我们系统地研究了奥密克戎变体感染的免疫学和代谢特征。我们发现奥密克戎变体能够抵抗针对野生型 SARS-CoV-2 受体结合域（RBD）的中和抗体。奥密克戎变体几乎不能被感染德尔塔变体的 2019 年冠状病毒病（COVID-19）康复者的血清中和。通过对 MHC 结合肽组学的质谱分析，我们发现与德尔塔相比，奥密克戎变体的刺突蛋白能产生额外的 CD8+T 细胞表位。这些表位能诱导强烈的 CD8+T 细胞反应。此外，我们发现加强接种能增加针对奥密克戎的交叉记忆 CD8+T 细胞反应。奥密克戎特异性 T 细胞的代谢调控组学分析显示，一种代谢特征能促进记忆 T 细胞的反应。一致地，奥密克戎刺激外周血单核细胞（PBMC）中存在更多的记忆 CD8+T 细胞。此外，CD147 也是奥密克戎变体的受体，CD147 抗体能抑制奥密克戎的感染。CD147 介导的奥密克戎在人 CD147 转基因小鼠模型中的感染会诱导渗出性肺泡肺炎。综上，我们的数据表明，疫苗加强针和受体阻断抗体是应对奥密克戎的两种有效策略。
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