Antiviral activities of sotrovimab against BQ.1.1 and XBB.1.5 in sera of treated patients
Bruel, T.; VRIGNAUD, L.-L.; PORROT, F.; STAROPOLI, I.; PLANAS, D.; GUIVEL-BENHASSINE, F.; PUECH, J.; PROT, M.; MUNIER, S.; BOLLAND, W.-H.; SOULIE, C.; ZAFILAZA, K.; LUSIVIKA-NZINGA, C.; MELEDJE, M.-L.; DORIVAL, C.; MOLINO, D.; PERE, H.; YORDANOV, Y.; SIMON-LORIERE, E.; David, V.; CARRAT, F.; SCHWARTZ, O.; MARCELIN, A.-G.; MARTIN-BLONDEL, G.; ANRS 0003S CoCoPrev Study Group,
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BackgroundMonoclonal 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.
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