A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

  1. Chunyin Gu
  2. Xiaodan Cao
  3. Zongda Wang
  4. Xue Hu
  5. Yanfeng Yao
  6. Yiwu Zhou
  7. Peipei Liu
  8. Xiaowu Liu
  9. Ge Gao
  10. Xiao Hu
  11. Yecheng Zhang
  12. Zhen Chen
  13. Li Gao
  14. Yun Peng
  15. Fangfang Jia
  16. Chao Shan
  17. Li Yu
  18. Kunpeng Liu
  19. Nan Li
  20. Weiwei Guo
  21. Guoping Jiang
  22. Juan Min
  23. Jianjian Zhang
  24. Lu Yang
  25. Meng Shi
  26. Tianquan Hou
  27. Yanan Li
  28. Weichen Liang
  29. Guoqiao Lu
  30. Congyi Yang
  31. Yuting Wang
  32. Kaiwen Xia
  33. Zheng Xiao
  34. Jianhua Xue
  35. Xueyi Huang
  36. Xin Chen
  37. Haixia Ma
  38. Donglin Song
  39. Zhongzong Pan
  40. Xueping Wang
  41. Haibing Guo
  42. Hong Liang
  43. Zhiming Yuan
  44. Wuxiang Guan
  45. Su-Jun Deng

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Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.07.429299: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All animal experiments were approved by the Institutional Animal Care and Use Committee of Wuhan Institute of Virology, Chinese Academy of Sciences (Ethics no. WIVA42202006).
    RandomizationAll animals were randomly divided into three groups: the control group (one animal, C1), prophylactic group (two animals, PA1 and PA2), and therapeutic group (two animals, AC1 and AC2).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Next, the libraries were labeled with streptavidin (SA)-phycoerythrin (PE) (eBioscience, 12-4317-8) and goat anti-mouse-Alexa Fluor 647 antibodies (Thermo Fisher Scientific, A-21235).
    SA)-phycoerythrin ( PE
    suggested: None
    anti-mouse-Alexa Fluor 647
    suggested: None
    Measurement of antibody affinity by BLI: The affinity of mAbs for SARS-CoV-2 RBD/S1 and its mutants (SARS-CoV-2 RBD [ACRO, SPD-C52H3], SARS-CoV-2 S1 [ACRO, S1N-C52H4],
    SARS-CoV-2
    suggested: None
    RBD/S1
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero E6 cells (ATCC, CRL-1586) were seeded in a 24-well plate (105 cells/well) and incubated at 37°C, in 5% CO2 for 16 h.
    Vero E6
    suggested: None
    In brief, engineered CHO-K1 cells (100 μl/well) were seeded into 96-well plates at 5 × 105 cells/ml.
    CHO-K1
    suggested: None
    Software and Algorithms
    SentencesResources
    IC50 values were determined with Prism V8.0 software (GraphPad) using a four-parameter logistic curve fitting approach.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Finally, we collected the cell culture supernatants after 24 h of infection for viral RNA extraction with a QIAamp 96 Virus QIAcube HT Kit (Qiagen, 57731) and for viral RNA copy number detection in a CFX96 Touch Real-Time PCR Detection System (Bio-Rad Laboratories).
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Data were processed using GraphPad Prism software (V8.0).
    GraphPad Prism
    suggested: (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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.02.07.429299v2 on bioRxiv
  3. Version published to 10.1101/2021.02.07.429299v1 on bioRxiv