Efficient Neutralization of SARS-CoV-2 Omicron and Other VOCs by a Broad Spectrum Antibody 8G3
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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. We tested the Omicron neutralization efficacy of 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 displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed a dramatic decrease activity. Antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. The in vivo results showed that Omicron virus was less virulent than the WA1/2020 strain, but still caused deterioration of health and even death in mice. Treatment with 8G3 quickly cleared virus load of mice. Antibody 8G3 also showed excellent activity against other variants of concern (VOCs), especially more efficient against authentic Delta plus virus. 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.
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SciScore for 10.1101/2022.02.25.482049: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Using S1-mFc recombinant protein (Sino Biological) as the primary antibody and FITC-labeled goat anti-mouse IgG antibody (Jackson) as the secondary antibody, the cells in the top 1% of fluorescence intensity were obtained on a BD FACSJazz cell sorter (BD). anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 293T-ACE2 cells: Human ACE2 protein was stably expressed on the surface of HEK-293T cells (ATCC) to obtain the 293T-ACE2 cells. HEK-293Tsuggested: NoneFor … SciScore for 10.1101/2022.02.25.482049: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Using S1-mFc recombinant protein (Sino Biological) as the primary antibody and FITC-labeled goat anti-mouse IgG antibody (Jackson) as the secondary antibody, the cells in the top 1% of fluorescence intensity were obtained on a BD FACSJazz cell sorter (BD). anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 293T-ACE2 cells: Human ACE2 protein was stably expressed on the surface of HEK-293T cells (ATCC) to obtain the 293T-ACE2 cells. HEK-293Tsuggested: NoneFor testing pseudovirus neutralizing activity by antibodies, 293T-ACE2 cells were seeded into a white 96-well plate (Corning) at a density of 1 × 104 per well, and cultured overnight at 37 °C with 5% CO2. 293T-ACE2suggested: NoneThus, the infection of the virus can be assessed by monitoring the CPE of the monolayer Vero E6 cells27,28. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Viruses (US_WA-1/2020 isolate; Omicron: clinically isolated, TVP 23328/SARS-CoV-2, strain EHC_C19_2811c, originally derived from Emory University by Mehul Suthar) in 100 particles per sample was subsequently added in duplicate. EHC_C19_2811csuggested: NoneRecombinant DNA Sentences Resources The ACE2 gene was inserted into the pHIV-puro plasmid, and prepared together with the packaging plasmids psPAX2 and VSV-G using an Endo-free Plasmid Mini Kit (Omega). pHIV-purosuggested: NonepsPAX2suggested: RRID:Addgene_12260)VSV-Gsuggested: RRID:Addgene_138479)Pseudovirus packaging and neutralization: The S sequences of SARS-CoV-2 (GenBank: QHD43416.1) or variants with intracellular 21 residue deletion were inserted into the pMD2G plasmid. pMD2Gsuggested: NoneA luciferase gene was constructed into plasmid pLVX-N1 as a reporter. pLVX-N1suggested: NoneSoftware and Algorithms Sentences Resources Data were analyzed using GraphPad Prism software, and the IC50 values were calculated using a four-parameter nonlinear regression function. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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