Antibody landscape against SARS-CoV-2 proteome reveals significant differences between non-structural/ accessory proteins and structural proteins

Li, Yang; Xu, Zhaowei; Lei, Qing; Lai, Dan-yun; Hou, Hongyan; Jiang, He-wei; Zheng, Yun-xiao; Wang, Xue-ning; Wu, Jiaoxiang; Ma, Ming-liang; Zhang, Bo; Chen, Hong; Yu, Caizheng; Xue, Jun-biao; Zhang, Hai-nan; Qi, Huan; Guo, Shu-juan; Zhang, Yandi; Lin, Xiaosong; Yao, Zongjie; Sheng, Huiming; Sun, Ziyong; Wang, Feng; Fan, Xionglin; Tao, Sheng-ce

The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collect 2,360 COVID-19 sera and 601 control sera. We analyze these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. Non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death is observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.