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Virology . Multiple exposures to SARS-CoV-2 Spike enhance cross-reactive antibody-dependent cellular cytotoxicity against SARS-CoV-1

tetano

Editor, Senior Moderator
Virology


. 2025 Mar 22:607:110512.
doi: 10.1016/j.virol.2025.110512. Online ahead of print. Multiple exposures to SARS-CoV-2 Spike enhance cross-reactive antibody-dependent cellular cytotoxicity against SARS-CoV-1

Guillaume Beaudoin-Bussières[SUP] 1 [/SUP], Alexandra Tauzin[SUP] 1 [/SUP], Katrina Dionne[SUP] 1 [/SUP], Omar El Ferri[SUP] 2 [/SUP], Mehdi Benlarbi[SUP] 1 [/SUP], Catherine Bourassa[SUP] 3 [/SUP], Halima Medjahed[SUP] 3 [/SUP], Renée Bazin[SUP] 4 [/SUP], Marceline Côté[SUP] 2 [/SUP], Andrés Finzi[SUP] 5 [/SUP]



Affiliations
Abstract

Vaccination or infection by SARS-CoV-2 elicits a protective immune response against severe outcomes. It has been reported that SARS-CoV-2 infection or vaccination elicits cross-reactive antibodies against other betacoronaviruses. While plasma neutralizing capacity was studied in great detail, their Fc-effector functions remain understudied. Here, we analyzed Spike recognition, neutralization and antibody-dependent cellular cytotoxicity (ADCC) against D614G, a recent Omicron subvariant of SARS-CoV-2 (JN.1) and SARS-CoV-1. Plasma from individuals before their first dose of mRNA vaccine, and following their second, third and sixth doses were analyzed. Despite poor neutralization activity observed after the second and third vaccine doses, ADCC was readily detected. By the sixth dose, individuals could neutralize and mediate ADCC against JN.1 and SARS-CoV-1. Since previous reports have shown that Fc-effector functions were associated with survival from acute infection, these results suggest that ADCC could help in combating future SARS-CoV-2 variants as well as closely related coronaviruses.

Keywords: ADCC; Coronavirus; Fc-effector functions; Omicron; SARS-CoV-1; SARS-CoV-2; Spike.

 
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