Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

  1. Paulina Kaplonek
  2. Deniz Cizmeci
  3. Stephanie Fischinger
  4. Ai-ris Collier
  5. Todd Suscovich
  6. Caitlyn Linde
  7. Thomas Broge
  8. Colin Mann
  9. Fatima Amanat
  10. Diana Dayal
  11. Justin Rhee
  12. Michael de St. Aubin
  13. Eric J. Nilles
  14. Elon R. Musk
  15. Anil S. Menon
  16. Erica Ollmann Saphire
  17. Florian Krammer
  18. Douglas A. Lauffenburger
  19. Dan H. Barouch
  20. Galit Alter

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Abstract

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

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    SciScore for 10.1101/2021.08.31.458247: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study populations: mRNA-vaccinated hospital staff: The Beth Israel Deaconess Medical Center institutional review board approved this study (#2021P000344) and the parent biorepository study (#2020P000361); participants provided written informed consent.
    Consent: Study populations: mRNA-vaccinated hospital staff: The Beth Israel Deaconess Medical Center institutional review board approved this study (#2021P000344) and the parent biorepository study (#2020P000361); participants provided written informed consent.
    Sex as a biological variableThe median age of the seropositive population was 32 years (range 19–62 years), and 84% were males.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Luminex profiling: Serum samples were analyzed by customized Luminex assay to quantify the relative concentration of antigen-specific antibody isotypes, subclasses, and Fcγ-receptor (FcγR) binding profiles, as previously described 46, 47.
    antigen-specific
    suggested: None
    Unbound antibodies were washed away, and antigen-bound antibodies were detected by using a PE-coupled detection antibody for each subclass and isotype (IgG1, IgG3, IgA1, and IgM; Southern Biotech), and Fcγ-receptors were fluorescently labeled with PE before addition to immune complexes (FcγR2a, FcγR3a; Duke Protein Production facility).
    antigen-bound
    suggested: None
    IgG1
    suggested: None
    IgG3
    suggested: None
    IgA1
    suggested: None
    PE median fluorescent intensity (MFI) is reported as a readout for antigenspecific antibody titers.
    antigenspecific
    suggested: None
    In order to measure antibody-dependent deposition of C3, lyophilized guinea pig complement (Cedarlane) was diluted in gelatin veronal buffer with calcium and magnesium (GBV++) (Boston BioProducts) and added to immune complexes.
    C3
    suggested: None
    Subsequently, C3 was detected with an anti-C3 fluorescein-conjugated goat IgG fraction detection antibody (Mpbio).
    anti-C3 fluorescein-conjugated goat IgG
    suggested: None
    Antibody-dependent cellular (ADCP) and neutrophil (ADNP) phagocytosis: Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent neutrophil phagocytosis (ADNP) were conducted according to the previously described protocols 50, 51.
    Antibody-dependent cellular ( ADCP
    suggested: None
    Antibody-dependent cellular phagocytosis ( ADCP )
    suggested: None
    antibody-dependent neutrophil phagocytosis ( ADNP
    suggested: None
    A magnet was used to separate beads with surfaces-bounded RBD-specific antibodies from the RBD-specific antibodies-depleted supernatant.
    antibodies-depleted supernatant.
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For ADCP, the immune complexes were incubated for 16-18 hours with THP-1 cells (1.25×105 THP-1 cells/mL) and for ADNP for 1 hour with RBC-lyzed whole blood.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    Both studies were approved by the Massachusetts General Brigham Healthcare (previously Partners Healthcare) Institutional Review Board.
    Partners Healthcare
    suggested: (Partners HealthCare Biobank, RRID:SCR_001316)
    The Flow cytometry was performed with 5 Laser LSR Fortessa Flow Cytometer and analysis was performed using FlowJo V10.7.1
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    All other figures were generated using ggplot2 54.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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.

  4. Version published to 10.1101/2021.08.31.458247v1 on bioRxiv