tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Jan 17;3(2):100510.
doi: 10.1016/j.xcrm.2022.100510. eCollection 2022 Feb 15.
SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity
Simone I Richardson[SUP] 1 2 [/SUP], Nelia P Manamela[SUP] 1 2 [/SUP], Boitumelo M Motsoeneng[SUP] 1 2 [/SUP], Haajira Kaldine[SUP] 1 2 [/SUP], Frances Ayres[SUP] 1 2 [/SUP], Zanele Makhado[SUP] 1 2 [/SUP], Mathilda Mennen[SUP] 3 [/SUP], Sango Skelem[SUP] 3 [/SUP], Noleen Williams[SUP] 3 [/SUP], Nancy J Sullivan[SUP] 4 [/SUP], John Misasi[SUP] 4 [/SUP], Glenda G Gray[SUP] 5 [/SUP], Linda-Gail Bekker[SUP] 6 [/SUP], Veronica Ueckermann[SUP] 7 [/SUP], Theresa M Rossouw[SUP] 8 [/SUP], Michael T Boswell[SUP] 7 [/SUP], Ntobeko A B Ntusi[SUP] 9 3 10 11 [/SUP], Wendy A Burgers[SUP] 9 12 11 [/SUP], Penny L Moore[SUP] 1 2 9 13 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.
Keywords: Ad26.COV2.S; Beta; Delta; Fc effector function; SARS-CoV-2; variant of concern
. 2022 Jan 17;3(2):100510.
doi: 10.1016/j.xcrm.2022.100510. eCollection 2022 Feb 15.
SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity
Simone I Richardson[SUP] 1 2 [/SUP], Nelia P Manamela[SUP] 1 2 [/SUP], Boitumelo M Motsoeneng[SUP] 1 2 [/SUP], Haajira Kaldine[SUP] 1 2 [/SUP], Frances Ayres[SUP] 1 2 [/SUP], Zanele Makhado[SUP] 1 2 [/SUP], Mathilda Mennen[SUP] 3 [/SUP], Sango Skelem[SUP] 3 [/SUP], Noleen Williams[SUP] 3 [/SUP], Nancy J Sullivan[SUP] 4 [/SUP], John Misasi[SUP] 4 [/SUP], Glenda G Gray[SUP] 5 [/SUP], Linda-Gail Bekker[SUP] 6 [/SUP], Veronica Ueckermann[SUP] 7 [/SUP], Theresa M Rossouw[SUP] 8 [/SUP], Michael T Boswell[SUP] 7 [/SUP], Ntobeko A B Ntusi[SUP] 9 3 10 11 [/SUP], Wendy A Burgers[SUP] 9 12 11 [/SUP], Penny L Moore[SUP] 1 2 9 13 [/SUP]
Affiliations
- PMID: 35233544
- PMCID: PMC8761540
- DOI: 10.1016/j.xcrm.2022.100510
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.
Keywords: Ad26.COV2.S; Beta; Delta; Fc effector function; SARS-CoV-2; variant of concern