Seroneutralization of Omicron BA.1 and BA.2 in patients receiving anti-SARS-CoV-2 monoclonal antibodies

Author:

Bruel Timothée,Hadjadj Jérôme,Maes Piet,Planas DelphineORCID,Seve Aymeric,Staropoli Isabelle,Guivel-Benhassine Florence,Porrot Françoise,Bolland William-Henry,Nguyen Yann,Casadevall Marion,Charre Caroline,Péré Hélène,Veyer David,Prot Matthieu,Baidaliuk Artem,Cuypers Lize,Planchais Cyril,Mouquet Hugo,Baele Guy,Mouthon Luc,Hocqueloux Laurent,Simon-Loriere Etienne,André Emmanuel,Terrier BenjaminORCID,Prazuck Thierry,Schwartz Olivier

Abstract

AbstractThe SARS-CoV-2 Omicron BA.1 variant has been supplanted in many countries by the BA.2 sub-lineage. BA.2 differs from BA.1 by about 21 mutations in its spike. Human anti-spike monoclonal antibodies (mAbs) are used for prevention or treatment of COVID-19. However, the capacity of therapeutic mAbs to neutralize BA.1 and BA.2 remains poorly characterized. Here, we first compared the sensitivity of BA.1 and BA.2 to neutralization by 9 therapeutic mAbs. In contrast to BA.1, BA.2 was sensitive to Cilgavimab, partly inhibited by Imdevimab and resistant to Adintrevimab and Sotrovimab. Two combinations of mAbs, Ronapreve (Casirivimab + Imdevimab) and Evusheld (Cilgavimab + Tixagevimab), are indicated as a pre-exposure prophylaxis in immunocompromised persons at risk of severe disease. We analyzed sera from 29 such individuals, up to one month after administration of Ronapreve and/or Evusheld. After treatment, all individuals displayed elevated antibody levels in their sera and neutralized Delta with high titers. Ronapreve recipients did not neutralize BA.1 and weakly impaired BA.2. With Evusheld, neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 patients, respectively. As compared to Delta, titers were more severely decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 participants. Therefore, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients’ sera, a phenomenon associated with decreased clinical efficacy.

Publisher

Cold Spring Harbor Laboratory

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