tetano
Editor, Senior Moderator
Virol J
. 2025 Feb 24;22(1):45.
doi: 10.1186/s12985-025-02667-0. NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants
Qi Gui[SUP] #[/SUP][SUP] 1 2 [/SUP], Haiyan Wang[SUP] #[/SUP][SUP] 2 [/SUP], Congcong Liu[SUP] #[/SUP][SUP] 2 [/SUP], Wenting Li[SUP] 2 [/SUP], Bing Zhou[SUP] 2 [/SUP], Shilong Tang[SUP] 2 [/SUP], Qing Fan[SUP] 2 [/SUP], Xiangyang Ge[SUP] 2 [/SUP], Bin Ju[SUP] 3 4 [/SUP], Zheng Zhang[SUP] 5 6 7 8 [/SUP]
Affiliations
SARS-CoV-2 infection widely induces antibody response targeting diverse viral proteins, including typical representative N-terminal domain (NTD), receptor-binding domain (RBD), and S2 subunit of spike. A lot of NTD-, RBD-, and S2-specific monoclonal antibodies (mAbs) have been isolated from COVID-19 convalescents, some of which displaying potent activities to inhibit viral infection. However, a small portion of NTD-specific mAbs elicited by wild-type (WT) SARS-CoV-2 primary infection could facilitate the virus entry into target cells in vitro, so called NTD-targeting infection-enhancing antibodies (NIEAs). To date, SARS-CoV-2 has evolved to massive variants carrying various NTD mutations, especially recent Omicron BA.2.86 and JN.1. In this study, we investigated whether these WT-NIEAs could still enhance the infectivity of emerging Omicron variants. Nine novel WT-NIEAs with diverse germline gene usage were identified from 3 individuals, effectively enlarging available antibody panel of NIEAs. Bivalent binding of NIEAs to inter-spike contributed to their infection-enhancing activities. WT-NIEAs could enhance the infectivity of SARS-CoV-2 variants emerged before Omicron, but ineffective to Omicron variants including BA.2.86 and JN.1, which was because of their changed antigenicity of NTDs. Overall, these data clearly demonstrated the cross-reactivity of these pre-existed WT-NIEAs to a series of SARS-CoV-2 variants, helping to evaluate the risk of enhanced infection of emerging variants in future.
Keywords: Cross-reactivity; Infection-enhancing activity; NIEAs; NTD; SARS-CoV-2 variants.
. 2025 Feb 24;22(1):45.
doi: 10.1186/s12985-025-02667-0. NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants
Qi Gui[SUP] #[/SUP][SUP] 1 2 [/SUP], Haiyan Wang[SUP] #[/SUP][SUP] 2 [/SUP], Congcong Liu[SUP] #[/SUP][SUP] 2 [/SUP], Wenting Li[SUP] 2 [/SUP], Bing Zhou[SUP] 2 [/SUP], Shilong Tang[SUP] 2 [/SUP], Qing Fan[SUP] 2 [/SUP], Xiangyang Ge[SUP] 2 [/SUP], Bin Ju[SUP] 3 4 [/SUP], Zheng Zhang[SUP] 5 6 7 8 [/SUP]
Affiliations
- PMID: 39994733
- PMCID: PMC11849304
- DOI: 10.1186/s12985-025-02667-0
SARS-CoV-2 infection widely induces antibody response targeting diverse viral proteins, including typical representative N-terminal domain (NTD), receptor-binding domain (RBD), and S2 subunit of spike. A lot of NTD-, RBD-, and S2-specific monoclonal antibodies (mAbs) have been isolated from COVID-19 convalescents, some of which displaying potent activities to inhibit viral infection. However, a small portion of NTD-specific mAbs elicited by wild-type (WT) SARS-CoV-2 primary infection could facilitate the virus entry into target cells in vitro, so called NTD-targeting infection-enhancing antibodies (NIEAs). To date, SARS-CoV-2 has evolved to massive variants carrying various NTD mutations, especially recent Omicron BA.2.86 and JN.1. In this study, we investigated whether these WT-NIEAs could still enhance the infectivity of emerging Omicron variants. Nine novel WT-NIEAs with diverse germline gene usage were identified from 3 individuals, effectively enlarging available antibody panel of NIEAs. Bivalent binding of NIEAs to inter-spike contributed to their infection-enhancing activities. WT-NIEAs could enhance the infectivity of SARS-CoV-2 variants emerged before Omicron, but ineffective to Omicron variants including BA.2.86 and JN.1, which was because of their changed antigenicity of NTDs. Overall, these data clearly demonstrated the cross-reactivity of these pre-existed WT-NIEAs to a series of SARS-CoV-2 variants, helping to evaluate the risk of enhanced infection of emerging variants in future.
Keywords: Cross-reactivity; Infection-enhancing activity; NIEAs; NTD; SARS-CoV-2 variants.