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

Author

Listed:
  • Delphine Planas

    (Université Paris Cité
    Vaccine Research Institute)

  • Timothée Bruel

    (Université Paris Cité
    Vaccine Research Institute)

  • 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
    Universitat de València)

  • Hugo Mouquet

    (Université Paris Cité)

  • Emmanuel André

    (University Hospitals Leuven, Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens
    Laboratory of Clinical Microbiology)

  • Laurent Hocqueloux

    (Service de Maladies Infectieuses)

  • Etienne Simon-Loriere

    (Université Paris Cité)

  • David Veyer

    (Hôpital Européen Georges Pompidou
    Université de Paris, Sorbonne Université)

  • Thierry Prazuck

    (Service de Maladies Infectieuses)

  • Hélène Péré

    (Hôpital Européen Georges Pompidou
    Université de Paris, Sorbonne Université)

  • Olivier Schwartz

    (Université Paris Cité
    Vaccine Research Institute)

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.

Suggested Citation

  • Delphine Planas & Timothée Bruel & Isabelle Staropoli & Florence Guivel-Benhassine & Françoise Porrot & Piet Maes & Ludivine Grzelak & Matthieu Prot & Said Mougari & Cyril Planchais & Julien Puech & M, 2023. "Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36561-6
    DOI: 10.1038/s41467-023-36561-6
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