Efficient Neutralization of SARS-CoV-2 Omicron and Other VOCs by a Broad Spectrum Antibody 8G3

Abstract

Numerous mutations in the spike protein of SARS-CoV-2 B.1.1.529 Omicron variant pose a crisis for antibody-based immunotherapies. The efficacy of emergency use authorized (EUA) antibodies that developed in early SARS-CoV-2 pandemic seems to be in flounder. In this work, we examined the Omicron variant neutralization using an early B cell antibody repertoire as well as several EUA antibodies in pseudovirus and authentic virus systems. More than half of the antibodies in the repertoire that showed good activity against WA1/2020 previously had completely lost neutralizing activity against Omicron, while antibody 8G3 from our early B cell repertoire displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab neutralized authentic WA1/2020 virus with low half maximal inhibitory concentration (IC50) values, but were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed activity but with a dramatic decrease. Interestingly, antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. 8G3 also showed excellent activity against other variants of concern (VOCs). Collectively, our results suggest that neutralizing antibodies with breadth remains broad neutralizing activity in tackling SARS-CoV-2 infection despite the universal evasion from EUA antibodies by Omicron variant.

Monoclonal antibody therapies against SARS-CoV-2

“… The classification into clusters by Brouwer and colleagues 45 is not included here because the authors only deposited electron microscopy data to the EMDB ( https://www.ebi.ac.uk/emdb/ ), but did not deposit structural information to the Protein Data Bank ( https://www.rcsb.org/ ). Monoclonal antibodies without a solved structure (ie, with no Protein Data Bank entry) are: 8G3, 46 upanovimab (SCTA01), 47 4-19, 48 2-17, 48 910-30, 49 S2X58, 33 1-20, 48 4-18, 48 5-7, 48 5-24, 48 2-7, 48 P2C-1A3, 50 2-15, 48 ABP-310, 51 VacW-209, 52 STI-9167, 53 10-40, 54 and TY027 ( NCT04649515 ; terminated due to low recruitment rate). An EMDB entry is available for S2X35, 25 2-36, 48 2-43, 48 and 4-8.…”

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster

“…To evaluate the intact antigenicity of the S mutant (S Δ21 ) encoded by the VSV vector, recognition activities of S Δ21 with hACE2 were characterized with specific neutralizing monoclonal antibodies. Among them, 2G1 was the one recognizing WA1 strain epitope, whereas the REGN10987 or 8G3 NAbs recognize epitopes of Delta or Omicron strains and potently inhibit their infection respectively 29 , 30 , 31 . The IC 50 of these antibodies was calculated using S Δ21 -rVSV ΔG -GFP.…”

Mutational escape prevention by combination of four neutralizing antibodies that target RBD conserved regions and stem helix

“…HEK-293T cells with ACE2 receptor stable expression (ACE2-293T cells) were established as described in our previous report ( Ma et al, 2022b ; Ma et al, 2022a ; Tang et al, 2022 ). In brief, a lentiviral system harboring the sequence of ACE2 receptor gene (Genbank ID: NP_001358344.1) was transduced to HEK-293T cells (ATCC, CRL-3216) to attain ACE2-293T cells pool.…”