Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Martin‐Blondel, Guillaume; Marcelin, Anne–Geneviève; Soulié, Cathia; Kaisaridi, Sofia; Lusivika‐Nzinga, Clovis; Dorival, Céline; Nailler, Laura; Boston, Anaïs; Melenotte, Cléa; Cabie, André; Choquet, Christophe; Coustillères, François; Martellosio, Jean-Philippe; Gaube, Géraldine; Trinh-Duc, Albert; Ronchetti, Anne-Marie; Pourcher, Valérie; Chauveau, Marie; Lacombe, Karine; Peiffer-Smadja, Nathan; Housset, P; Perrot, Aurore; Pialoux, Gilles; Martin, Aurélie; Dubée, Vincent; Devaux, Mathilde; Frey, Jérôme; Cazanave, Charles; Liblau, Roland; Carrat, Fabrice; Yordanov, Youri

doi:10.1016/j.jinf.2022.06.033

Cited by 34 publications

(36 citation statements)

References 10 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 54 This ADCC activity may help understand why sotrovimab remains clinically active against BA.2 despite its very limited neutralization. 55 Similarly, it has been reported that non-neutralizing antibodies capable of mediating Fc-effector functions display some efficacy in animal models. 56 It may be worth examining whether a combination of sotrovimab and Evusheld or bebtelovimab may improve therapeutic efficacy of the mAbs.…”

Section: Discussionmentioning

confidence: 96%

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Bruel¹,

Stéfic²,

Nguyen³

et al. 2022

Cell Reports Medicine

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 96%

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Bruel¹,

Stéfic²,

Nguyen³

et al. 2022

Cell Reports Medicine

View full text Add to dashboard Cite

“…The most potent antibody to activate ADCC against Omicron sublineages was Sotrovimab, even if its neutralization IC50 was relatively high compared to other antibodies. This ADCC activity may help understand why Sotrovimab remains clinically active against BA.2, despite its very limited neutralization 51 . Similarly, it has been reported that non-neutralizing antibodies capable of mediating Fc-effector functions display some efficacy in animal models 52 .…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

Bruel

Stéfic

Nguyen

et al. 2022

Preprint

View full text Add to dashboard Cite

The emergence of novel Omicron lineages, such as BA.5, may impact the therapeutic efficacy of anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). Here, we evaluated the neutralization and ADCC activity of 6 therapeutic mAbs against Delta, BA.2, BA.4 and BA.5 isolates. The Omicron sub-variants escaped most of the antibodies but remained sensitive to Bebtelovimab and Cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 displayed identical neutralization profiles. Sotrovimab was the most efficient at eliciting ADCC. We also analyzed 121 sera from 40 immunocompromised individuals up to 6 months after infusion of 1200 mg of Ronapreve (Imdevimab + Casirivimab), and 300 or 600 mg of Evusheld (Cilgavimab + Tixagevimab). Sera from Ronapreve-treated individuals did not neutralize Omicron subvariants. Evusheld-treated individuals neutralized BA.2 and BA.5, but titers were reduced by 41- and 130-fold, respectively, compared to Delta. A longitudinal evaluation of sera from Evusheld-treated patients revealed a slow decay of mAb levels and neutralization. The decline was more rapid against BA.5. Our data shed light on the antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.

show abstract

“…Sotrovimab also displays non-neutralizing antiviral activities, including ADCC 51 52 . Sotrovimab remains clinically active against BA.2 53 . It will be of interest determining whether Sotrovimab could maintain some activity in vivo against these novel Omicron subvariants, despite reduced neutralization.…”

Section: Discussionmentioning

confidence: 99%

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

Planas

Bruel

Staropoli

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Cited by 34 publications

References 10 publications

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

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

Contact Info

Product

Resources

About