A new study shows that the Monoclonal antibodies by Regeneron, Lilly, and Celltrion completely lost neutralizing activity when faced with Omicron. However, those offered by AstraZeneca and Vir Biotechnology retained partial activity.
The researchers suggest that more research identifying monoclonal antibodies that target the most highly conserved residues on the SARS-CoV-2 spike protein is necessary for adequate protection against Omicron and other future variants.
Monoclonal antibody treatments —REGN10933, REGN10987, LY-CoV555, LV-CoV016, CT-P59 and SARS2-38 —had no effect against Omicron. There continued to be an absence of neutralizing activity when researchers tested antibodies at the highest concentration.
Other monoclonal antibodies showed a partial reduction in inhibitory activity. COV2-2130 and COV2-2196 had an approximate 12- to 150-fold decrease in neutralizing power against Omicron. In contrast, S309 showed a 2-fold reduction in neutralization.
Monoclonal antibody cocktails in current medical use — REGN10933/REGN10987 and LY112 CoV555/LV-CoV016 — had no effect against Omicron. Another cocktail, COV2-2130/COV2-2196, had about a 12-fold decrease in inhibitory activity.
Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein.
Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (∼12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.
The researchers suggest that more research identifying monoclonal antibodies that target the most highly conserved residues on the SARS-CoV-2 spike protein is necessary for adequate protection against Omicron and other future variants.
Monoclonal antibody treatments —REGN10933, REGN10987, LY-CoV555, LV-CoV016, CT-P59 and SARS2-38 —had no effect against Omicron. There continued to be an absence of neutralizing activity when researchers tested antibodies at the highest concentration.
Other monoclonal antibodies showed a partial reduction in inhibitory activity. COV2-2130 and COV2-2196 had an approximate 12- to 150-fold decrease in neutralizing power against Omicron. In contrast, S309 showed a 2-fold reduction in neutralization.
Monoclonal antibody cocktails in current medical use — REGN10933/REGN10987 and LY112 CoV555/LV-CoV016 — had no effect against Omicron. Another cocktail, COV2-2130/COV2-2196, had about a 12-fold decrease in inhibitory activity.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the development and deployment of highly effective antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy.Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein.
Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (∼12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.
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