Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Delphine Planas (1, 2) , Timothée Bruel (1, 2) , Isabelle Staropoli (1) , Florence Guivel-Benhassine (1) , Françoise Porrot (1) , Piet Maes (3) , Ludivine Grzelak (1) , Matthieu Prot (4) , Said Mougari (4) , Cyril Planchais (5) , Julien Puech (6) , Madelina Saliba (6) , Riwan Sahraoui (6) , Florent Fémy (6) , Nathalie Morel (7) , Jérémy Dufloo (8, 9) , Rafael Sanjuán (9) , Hugo Mouquet (5) , Emmanuel André (10, 3) , Laurent Hocqueloux (11) , Etienne Simon-Loriere (4) , David Veyer (6, 12) , Thierry Prazuck (11) , Hélène Péré (6, 12) , Olivier Schwartz (1, 2)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 VRI - Vaccine Research Institute [Créteil, France]
3 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
4 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
5 Immunologie humorale - Humoral Immunology
6 HEGP - Hôpital Européen Georges Pompidou [APHP]
7 SPI - Service de Pharmacologie et Immunoanalyse
8 I2SysBio (CSIC-UV)
9 UV - Universitat de València
10 University Hospitals Leuven [Leuven]
11 CHRO - Centre Hospitalier Régional d'Orléans
12 FunGeST - Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC]

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

Domaines: Sciences du Vivant [q-bio]

Delphine Planas, Timothée Bruel, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, et al.. Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies. bioRxiv : the preprint server for biology, 2022, ⟨10.1101/2022.11.17.516888⟩. ⟨pasteur-04082579⟩