Jiejie Geng,Xu Yang,Kun Wang,Ke Wang ORCID: orcid.org/0000-0001-8913-7115,Ruo Chen,Zhi-Nan Chen,Chuan Qin ORCID: orcid.org/0000-0002-6261-1232,Guizhen Wu,Youchun Wang ORCID: orcid.org/0000-0001-9769-5141,Ke Xu,Peng Du,Jiangning Liu,Shirui Chen,Tao Zhang,Xiuxuan Sun,Ting Guo,Ying Shi,Zheng Zhang,Ding Wei,Peng Lin,Qingyi Wang,Jing Yuan ORCID: orcid.org/0000-0002-8937-9568,Jiuxin Qu,Jin Zou,Yingxia Liu,Hongzhou Lu,Ping Zhu,Huijie Bian ORCID: orcid.org/0000-0003-4690-4622 &…Liang Chen

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.

https://doi.org/10.1038/s41392-022-01265-8

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