A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

  1. Alexandra Tauzin
  2. Manon Nayrac
  3. Mehdi Benlarbi
  4. Shang Yu Gong
  5. Romain Gasser
  6. Guillaume Beaudoin-Bussières
  7. Nathalie Brassard
  8. Annemarie Laumaea
  9. Dani Vézina
  10. Jérémie Prévost
  11. Sai Priya Anand
  12. Catherine Bourassa
  13. Gabrielle Gendron-Lepage
  14. Halima Medjahed
  15. Guillaume Goyette
  16. Julia Niessl
  17. Olivier Tastet
  18. Laurie Gokool
  19. Chantal Morrisseau
  20. Pascale Arlotto
  21. Leonidas Stamatatos
  22. Andrew T. McGuire
  23. Catherine Larochelle
  24. Pradeep Uchil
  25. Maolin Lu
  26. Walther Mothes
  27. Gaston De Serres
  28. Sandrine Moreira
  29. Michel Roger
  30. Jonathan Richard
  31. Valérie Martel-Laferrière
  32. Ralf Duerr
  33. Cécile Tremblay
  34. Daniel E. Kaufmann
  35. Andrés Finzi

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Abstract

The standard dosing of the Pfizer/BioNTech BNT162b2 mRNA vaccine validated in clinical trials includes two doses administered three weeks apart. While the decision by some public health authorities to space the doses because of limiting supply has raised concerns about vaccine efficacy, data indicate that a single dose is up to 90% effective starting 14 days after its administration. We analyzed humoral and T cells responses three weeks after a single dose of this mRNA vaccine. Despite the proven efficacy of the vaccine at this time point, no neutralizing activity were elicited in SARS-CoV-2 naïve individuals. However, we detected strong anti-receptor binding domain (RBD) and Spike antibodies with Fc-mediated effector functions and cellular responses dominated by the CD4 + T cell component. A single dose of this mRNA vaccine to individuals previously infected by SARS-CoV-2 boosted all humoral and T cell responses measured, with strong correlations between T helper and antibody immunity. Neutralizing responses were increased in both potency and breadth, with distinctive capacity to neutralize emerging variant strains. Our results highlight the importance of vaccinating uninfected and previously-infected individuals and shed new light into the potential role of Fc-mediated effector functions and T cell responses in vaccine efficacy. They also provide support to spacing the doses of two-vaccine regimens to vaccinate a larger pool of the population in the context of vaccine scarcity against SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.18.435972: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethics Statement: All work was conducted in accordance with the Declaration of Helsinki in terms of informed consent and approval by an appropriate institutional board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationAuthentication: The presence of the desired mutations was determined by automated DNA sequencing.

    Table 2: Resources

    Antibodies
    SentencesResources
    Alexa Fluor-647-conjugated goat anti-human Abs able to detect all Ig isotypes (anti-human IgM+IgG+IgA; Jackson ImmunoResearch Laboratories) were used as secondary antibodies to detect plasma binding in flow cytometry experiments.
    anti-human Abs
    suggested: None
    goat anti-human IgM+IgG+IgA Abs (1/800 dilution) were used as secondary antibodies.
    anti-human IgM+IgG+IgA
    suggested: None
    ADCC assay: For evaluation of anti-SARS-CoV-2 antibody-dependent cellular cytotoxicity (ADCC), parental CEM.
    anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus neutralization assay: 293T cells were transfected with the lentiviral vector pNL4.3 R-E-Luc (NIH AIDS Reagent Program) and a plasmid encoding for the indicated Spike glycoprotein (D614G, B.1.1.7, D614G/E484K, D614G/N501S, D614G/S477N, D614G/N501Y and SARS-CoV-1) at a ratio of 5:4.
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were performed using FlowJo v10.7.1 software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistics were analyzed using GraphPad Prism version 8.0.1 (GraphPad, San Diego, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Edge bundling graphs were generated in undirected mode in R and RStudio using ggraph, igraph, tidyverse, and RColorBrewer packages.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    RColorBrewer
    suggested: (RColorBrewer, RRID:SCR_016697)
    Line charts in overlay were created with Prism 8.4.3 using normalized data per response and Akima spline interpolation.
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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.

    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 10.1101/2021.03.18.435972 on bioRxiv