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Sotrovimab remains efficacious against the BQ.1.1 omicron subvariant of SARS-CoV-2

In a study published in Heliyon, researchers from IDMIT (CEA-Jacob) used a well-characterized non-human primate model to show that sotrovimab is efficacious against the BQ.1.1 subvariant of SARS-CoV-2. Their results lend support for the continued use of sotrovimab in patients ineligible for nirmatrelvir/ritonavir.

Published on 5 July 2023

The currently circulating omicron variants of SARS-CoV-2 have acquired novel mutations at the spike protein's receptor-binding domain, increasing their affinity for the ACE2 receptor located on the cell's surface. These variants thus show greater transmission capacity and an improved ability for escaping current neutralizing antibodies. The BA.5 subvariant BQ.1.1 is currently the principal variant circulating in Europe, and, like its other omicron siblings, it shows particular talent for skirting many of today's anti-SARS-CoV-2 antibody therapies—and clear answers on that point from research. For example, the authors of some recent in vitro studies have reported that sotrovimab (brand name: Xevudy), a monoclonal antibody targeted to SARS-CoV-2's spike protein, conserves its activity against omicron subvariants, whereas others have underlined drastic reductions in inhibition, including for the BQ.1.1 subvariant. In vivo however, sotrovimab has been shown to protect against BQ.1.1 infection in mouse and hamster models.

To help resolve these contradictory results and bring new possibilities to physicians, researchers from IDMIT (UMRU1184/ImVa-HB), Institut Pasteur and the Emergent Viruses Unit at Aix-Marseille University joined forces to evaluate the BQ.1.1 prophylactic efficacy of sotrovimab in a well-characterized non-human primate model. The team followed an experimental protocol previously deployed for other variants. Post-administration sotrovimab serum assay furnished results similar to those obtained in humans in the COMET-ICE clinical trial, which was aimed at evaluating sotrovimab efficacy in earlier SARS-CoV-2 variants. RT-PCR quantification detected viral genomic RNA in control animals, but not in the treated animals, suggesting that sotrovimab was efficacious against viral replication.

Sotrovimab had been deauthorized because of its poor in vitro efficacy against omicron variants. However, this new study demonstrated its prophylactic efficacy for the BQ.1.1 subvariant, against which it stopped viral replication in both the upper and lower airways in a non-human primate model. These results, published in Heliyon, confirm the interest of sotrovimab in this setting and thus argue in favor of its use in patients who are ineligible for nirmatrelvir/ritonavir (brand name: Paxlovid). Further studies will be necessary to confirm its potential as a treatment for BQ.1.1 subvariant COVID-19.

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