Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

  1. Liane Dupont
  2. Luke B. Snell
  3. Carl Graham
  4. Jeffrey Seow
  5. Blair Merrick
  6. Thomas Lechmere
  7. Thomas J. A. Maguire
  8. Sadie R. Hallett
  9. Suzanne Pickering
  10. Themoula Charalampous
  11. Adela Alcolea-Medina
  12. Isabella Huettner
  13. Jose M. Jimenez-Guardeño
  14. Sam Acors
  15. Nathalia Almeida
  16. Daniel Cox
  17. Ruth E. Dickenson
  18. Rui Pedro Galao
  19. Neophytos Kouphou
  20. Marie Jose Lista
  21. Ana Maria Ortega-Prieto
  22. Harry Wilson
  23. Helena Winstone
  24. Cassandra Fairhead
  25. Jia Zhe Su
  26. Gaia Nebbia
  27. Rahul Batra
  28. Stuart Neil
  29. Manu Shankar-Hari
  30. Jonathan D. Edgeworth
  31. Michael H. Malim
  32. Katie J. Doores

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Abstract

COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 individuals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from individuals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants.

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  1. Version published to 10.1038/s41564-021-00974-0
  2. ScreenIT

    SciScore for 10.1101/2021.06.07.21258351: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 pseudotyped virus particle preparation: Pseudotyped HIV virus incorporating the SARS-CoV-2 Spike protein (either wild-type, B.1.1.7, P.1, B.1.351) was produced in a 10 cm dish seeded the day prior with 5×106 HEK293T/17 cells in 10 ml of complete Dulbecco’s Modified Eagle’s Medium (DMEM-C, 10% FBS and 1% Pen/Strep) containing 10% (vol/vol)
    HEK293T/17
    suggested: None
    Next, Hela cells stably expressing the ACE2 receptor were added (10,000 cells/25µL per well) and the plates were left for 72 hours.
    Hela
    suggested: None
    Recombinant DNA
    SentencesResources
    Spikes encoding the variants B.1.351 and P.1 were synthesized (Genewiz, USA) and cloned into pcDNA3.1. B.1.351 mutations introduced were L18F, D80A, D215G, Delta242-244, R246I, K417N, E484K, N501Y, D614G, A701V. P.1 mutations introduced were L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F.
    pcDNA3.1
    suggested: RRID:Addgene_79663)

    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.
    • 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.

    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.

  3. Version published to 10.1101/2021.06.07.21258351v1 on medRxiv