NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants

• DOI: 10.1186/s12985-025-02667-0
• Publication Date: 2025-02-24T06:09:51Z
• Authors: Qi Gui; Haiyan Wang; Congcong Liu; Wenting Li; Bing Zhou; Shilong Tang; Qing Fan; Xiangyang Ge; Bin Ju; Zheng Zhang
• Keywords: Infectivity; 2019-20 coronavirus outbreak

SARS-CoV-2 infection widely induces antibody response targeting diverse viral proteins, including typical representative N-terminal domain (NTD), receptor-binding (RBD), and S2 subunit of spike. A lot NTD-, RBD-, S2-specific monoclonal antibodies (mAbs) have been isolated from COVID-19 convalescents, some which displaying potent activities to inhibit infection. However, a small portion NTD-specific mAbs elicited by wild-type (WT) primary could facilitate the virus entry into target cells in vitro, so called NTD-targeting infection-enhancing (NIEAs). To date, has evolved massive variants carrying various NTD mutations, especially recent Omicron BA.2.86 JN.1. In this study, we investigated whether these WT-NIEAs still enhance infectivity emerging variants. Nine novel with germline gene usage were identified 3 individuals, effectively enlarging available panel NIEAs. Bivalent binding NIEAs inter-spike contributed their activities. emerged before Omicron, but ineffective JN.1, was because changed antigenicity NTDs. Overall, data clearly demonstrated cross-reactivity pre-existed series variants, helping evaluate risk enhanced future. Additional 9 individuals infected SARS-CoV-2. This Fc-independent enhancement mediated divalent F(ab')2 not Changed led ineffectiveness WT-induced