Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Bruel, Timothee; Stefic, Karl; Nguyen, Yann; Toniutti, Donatella; Staropoli, Isabelle; Porrot, Francoise; Guivel-Benhassine, Florence; Bolland, William-Henry; Planas, Delphine; Hadjadj, Jerome; Handala, Lynda; Planchais, Cyril; Prot, Matthieu; Simon-Loriere, Etienne; Andre, Emmanuel; Baele, Guy; Cuypers, Lize; Mouthon, Luc; Mouquet, Hugo; Buchrieser, Julian; Seve, Aymeric; Prazuck, Thierry; Maes, Piet; Terrier, Benjamin; Hocqueloux, Laurent; Schwartz, Olivier

doi:10.1016/j.xcrm.2022.100850

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Author:

Bruel, Timothee

Stefic, Karl ; Nguyen, Yann ; Toniutti, Donatella ; Staropoli, Isabelle ; Porrot, Francoise ; Guivel-Benhassine, Florence ; Bolland, William-Henry ; Planas, Delphine ; Hadjadj, Jerome ; Handala, Lynda ; Planchais, Cyril ; Prot, Matthieu ; Simon-Loriere, Etienne ; Andre, Emmanuel ; Baele, Guy ; Cuypers, Lize ; Mouthon, Luc ; Mouquet, Hugo ; Buchrieser, Julian ; Seve, Aymeric ; Prazuck, Thierry ; Maes, Piet ; Terrier, Benjamin ; Hocqueloux, Laurent ; Schwartz, Olivier

Keywords:

Science & Technology, Life Sciences & Biomedicine, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, EFFECTOR FUNCTIONS, SUBVARIANTS, ADCC, Omicron, SARS-CoV-2, antibodies, neutralization, Humans, COVID-19, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Antiviral Agents, G0H4420N#56116093, C14/18/094#54689608, G098321N#56127204, 32 Biomedical and clinical sciences

Abstract:

The emergence of Omicron sublineages impacts the therapeutic efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs). Here, we evaluate neutralization and antibody-dependent cellular cytotoxicity (ADCC) activities of 6 therapeutic mAbs against Delta, BA.2, BA.4, and BA.5. The Omicron subvariants escape most antibodies but remain sensitive to bebtelovimab and cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 display identical neutralization profiles. Sotrovimab is the most efficient at eliciting ADCC. We also analyze 121 sera from 40 immunocompromised individuals up to 6 months after infusion of Ronapreve (imdevimab + casirivimab) or Evusheld (cilgavimab + tixagevimab). Sera from Ronapreve-treated individuals do not neutralize Omicron subvariants. Evusheld-treated individuals neutralize BA.2 and BA.5, but titers are reduced. A longitudinal evaluation of sera from Evusheld-treated patients reveals a slow decay of mAb levels and neutralization, which is faster against BA.5. Our data shed light on antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.