Antiviral activities of sotrovimab against BQ.1.1 and XBB.1.5 in sera of treated patients

Author:

Bruel TimothéeORCID,Vrignaud Lou-Léna,Porrot Françoise,Staropoli Isabelle,Planas Delphine,Guivel-Benhassine Florence,Puech Julien,Prot Matthieu,Munier Sandie,Henry-Bolland William,Soulié Cathia,Zafilaza Karen,Lusivika-Nzinga Clovis,Meledge Marie-Laure,Dorival Céline,Molino Diana,Péré Hélène,Yordanov Youri,Simon-Lorière Etienne,Veyer David,Carrat Fabrice,Schwartz Olivier,Marcelin Anne-Geneviève,Martin-Blondel Guillaume,

Abstract

AbstractBackgroundMonoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.1 and XBB.1.5 evade neutralization of therapeutic mAbs, leading to recommendations against their use. Yet, the antiviral activities of mAbs in treated patients remain ill-defined.MethodsWe investigated neutralization and antibody-dependent cellular cytotoxicity (ADCC) of D614G, BQ.1.1 and XBB.1.5 in 320 sera from 80 immunocompromised patients with mild-to-moderate COVID-19 prospectively treated with mAbs (sotrovimab, n=29; imdevimab/casirivimab, n=34; cilgavimab/tixagevimab, n=4) or anti-protease (nirmatrelvir/ritonavir, n=13). We measured live-virus neutralization titers and quantified ADCC with a reporter assay.FindingsOnly Sotrovimab elicits serum neutralization and ADCC against BQ.1.1 and XBB.1.5. As compared to D614G, sotrovimab neutralization titers of BQ.1.1 and XBB.1.5 are reduced (71- and 58-fold, respectively), but ADCC levels are only slightly decreased (1.4- and 1-fold, for BQ.1.1 and XBB.1.5, respectively).InterpretationOur results show that sotrovimab is active against BQ.1.1 and XBB.1.5 in treated individuals, suggesting that it may be a valuable therapeutic option.

Publisher

Cold Spring Harbor Laboratory

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