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An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies

VanBlargan et al., bioRxiv, doi:10.1101/2021.12.15.472828
Dec 2021  
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22nd treatment shown to reduce risk in May 2021, now with p = 0.00036 from 21 studies, recognized in 7 countries. Efficacy is variant dependent.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 111 treatments. c19early.org
In vitro study (Vero-TMPRSS2 and Vero-hACE2-TMPRSS2) showing complete loss of inhibitory activity for B.1.1.529 omicron with LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59, ~12-fold decrease for COV2-2196/COV2-2130, and minimal change for S309.
Efficacy is highly variant dependent. In Vitro research suggests a lack of efficacy for omicron1-5.
Study covers casirivimab/imdevimab, bamlanivimab/etesevimab, and sotrovimab.
VanBlargan et al., 17 Dec 2021, preprint, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperBamlaniv../e..All
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies
Laura A Vanblargan, John M Errico, Peter J Halfmann, Seth J Zost, James E Crowe Jr, Lisa A Purcell, Yoshihiro Kawaoka, Davide Corti, Daved H Fremont, M.D Michael S Diamond
doi:10.1101/2021.12.15.472828
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.
AUTHOR CONTRIBUTIONS L
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