Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants

  1. Lingshu Wang
  2. Tongqing Zhou
  3. Yi Zhang
  4. Eun Sung Yang
  5. Chaim A. Schramm
  6. Wei Shi
  7. Amarendra Pegu
  8. Olamide K. Oloninyi
  9. Amy Ransier
  10. Samuel Darko
  11. Sandeep R. Narpala
  12. Christian Hatcher
  13. David R. Martinez
  14. Yaroslav Tsybovsky
  15. Emily Phung
  16. Olubukola M. Abiona
  17. Evan M. Cale
  18. Lauren A. Chang
  19. Kizzmekia S. Corbett
  20. Anthony T. DiPiazza
  21. Ingelise J. Gordon
  22. Kwanyee Leung
  23. Tracy Liu
  24. Rosemarie D. Mason
  25. Alexandra Nazzari
  26. Laura Novik
  27. Adam S. Olia
  28. Nicole A. Doria-Rose
  29. Tyler Stephens
  30. Christopher D. Stringham
  31. Chloe Adrienna Talana
  32. I-Ting Teng
  33. Danielle Wagner
  34. Alicia T. Widge
  35. Baoshan Zhang
  36. Mario Roederer
  37. Julie E. Ledgerwood
  38. Tracy J. Ruckwardt
  39. Martin R. Gaudinski
  40. Ralph S. Baric
  41. Barney S. Graham
  42. Adrian B. McDermott
  43. Daniel C. Douek
  44. Peter D. Kwong
  45. John R Mascola
  46. Nancy J. Sullivan
  47. John Misasi

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Abstract

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.1.7 and B.1.351 VOCs. Two of them are ultrapotent, with sub-nanomolar neutralization titers (IC 50 <0.0006 to 0.0102 μg/mL; IC80 < 0.0006 to 0.0251 μg/mL). We define the structural and functional determinants of binding for all four VOC-targeting antibodies, and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting potential means to mitigate resistance development. These results define the basis of therapeutic cocktails against VOCs and suggest that targeted boosting of existing immunity may increase vaccine breadth against VOCs.

One Sentence Summary

Ultrapotent antibodies from convalescent donors neutralize and mitigate resistance of SARS-CoV-2 variants of concern.

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  2. Rapid Reviews Infectious Diseases

    Naveenchandra Suryadevara, Robert Carnahan

    Review of "Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants"

    Reviewers: Naveenchandra Suryadevara, Robert Carnahan (Vanderbilt) | 📗📗📗📗◻️

  3. ScreenIT

    SciScore for 10.1101/2021.02.25.432969: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To do this, we superposed the antibody-RBD complex structures of CB6 (PDB ID 7C01) (25), REGN10933 (PDB ID 6XDG) (26, 27) and LY-CoV555 (PDB ID 7KMG) (18) with the A23-58.1 structure over the RDB region.
    antibody-RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    Science (80-. ). 370, 950–957 (2020). 33. 5 34. 36. X. Shen, H. Tang, C. McDanal, K. Wagh, W. Fischer, J. Theiler, H. Yoon, D. Li, B. F. Haynes, K. O. Sanders, S. Gnanakaran, N. Hengartner, R. Pajon, G. Smith, F. Dubovsky, G. M. Glenn, B. Korber, D. C. Montefiori, bioRxiv, in press, 20 doi:10.1101/2021.01.27.428516. 37.
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    Results from OddPub: Thank you for sharing your data.

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    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.

  4. Version published to 10.1101/2021.02.25.432969 on bioRxiv