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

Delphine Planas (), Timothée Bruel, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, Piet Maes, Ludivine Grzelak, Matthieu Prot, Said Mougari, Cyril Planchais, Julien Puech, Madelina Saliba, Riwan Sahraoui, Florent Fémy, Nathalie Morel, Jérémy Dufloo, Rafael Sanjuán, Hugo Mouquet, Emmanuel André, Laurent Hocqueloux, Etienne Simon-Loriere, David Veyer, Thierry Prazuck, Hélène Péré and Olivier Schwartz ()
Additional contact information
Delphine Planas: Université Paris Cité
Timothée Bruel: Université Paris Cité
Isabelle Staropoli: Université Paris Cité
Florence Guivel-Benhassine: Université Paris Cité
Françoise Porrot: Université Paris Cité
Piet Maes: Laboratory of Clinical and Epidemiological Virology
Ludivine Grzelak: Université Paris Cité
Matthieu Prot: Université Paris Cité
Said Mougari: Université Paris Cité
Cyril Planchais: Université Paris Cité
Julien Puech: Hôpital Européen Georges Pompidou
Madelina Saliba: Hôpital Européen Georges Pompidou
Riwan Sahraoui: Hôpital Européen Georges Pompidou
Florent Fémy: Hôpital Européen Georges Pompidou
Nathalie Morel: Université Paris-Saclay
Jérémy Dufloo: Universitat de València-CSIC
Rafael Sanjuán: Universitat de València-CSIC
Hugo Mouquet: Université Paris Cité
Emmanuel André: University Hospitals Leuven, Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens
Laurent Hocqueloux: Service de Maladies Infectieuses
Etienne Simon-Loriere: Université Paris Cité
David Veyer: Hôpital Européen Georges Pompidou
Thierry Prazuck: Service de Maladies Infectieuses
Hélène Péré: Hôpital Européen Georges Pompidou
Olivier Schwartz: Université Paris Cité

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract 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 subvariant BQ.1.1 became predominant in many countries in December 2022. The subvariants 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) lose antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. BQ.1.1 is also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals are low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increases these titers, which remains about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increases more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitates their spread in immunized populations and raises concerns about the efficacy of most available mAbs.

Date: 2023
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DOI: 10.1038/s41467-023-36561-6

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