Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Olivier Schwartz (1, 2) , Thierry Prazuck (3) , Benjamin Terrier (4) , Emmanuel André (5, 6) , Etienne Simon-Loriere (7) , Laurent Hocqueloux (3) , Luc Mouthon (4) , Guy Baele (6) , Hugo Mouquet (8) , Cyril Planchais (8) , Lize Cuypers (5) , Artem Baidaliuk (7) , Matthieu Prot (7) , David Veyer (9, 10) , Hélène Péré (9, 10) , Caroline Charre (11, 12, 4) , Marion Casadevall (4) , Yann Nguyen (4) , William-Henry Bolland (1, 13) , Françoise Porrot (1) , Florence Guivel-Benhassine (1) , Isabelle Staropoli (1) , Aymeric Seve (3) , Delphine Planas (1, 2) , Piet Maes (6) , Jérôme Hadjadj (4) , Timothée Bruel (1, 2)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 VRI - Vaccine Research Institute
3 CHRO - Centre Hospitalier Régional d'Orléans
4 Hôpital Cochin [AP-HP]
5 University Hospitals Leuven [Leuven]
6 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
7 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
8 Immunologie humorale - Humoral Immunology
9 FunGeST - Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC]
10 HEGP - Hôpital Européen Georges Pompidou [APHP]
11 UPCité - Université Paris Cité
12 IC UM3 (UMR 8104 / U1016) - Institut Cochin
13 ED562 - BioSPC - École Doctorale Bio Sorbonne Paris Cité [Paris]

The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.

Domains: Virology

Olivier Schwartz, Thierry Prazuck, Benjamin Terrier, Emmanuel André, Etienne Simon-Loriere, et al.. Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies. Nature Medicine, 2022, ⟨10.1038/s41591-022-01792-5⟩. ⟨pasteur-03654237⟩