Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms

  1. Caroline G. Atyeo
  2. Lydia L. Shook
  3. Sara Brigida
  4. Rose M. De Guzman
  5. Stepan Demidkin
  6. Cordelia Muir
  7. Babatunde Akinwunmi
  8. Arantxa Medina Baez
  9. Maegan L. Sheehan
  10. Erin McSweeney
  11. Madeleine D. Burns
  12. Ruhi Nayak
  13. Maya K. Kumar
  14. Chinmay D. Patel
  15. Allison Fialkowski
  16. Dana Cvrk
  17. Ilona T. Goldfarb
  18. Lael M. Yonker
  19. Alessio Fasano
  20. Alejandro B. Balazs
  21. Michal A. Elovitz
  22. Kathryn J. Gray
  23. Galit Alter
  24. Andrea G. Edlow

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Abstract

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.

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  3. Version published to 10.1038/s41467-022-31169-8
  4. ScreenIT

    SciScore for 10.1101/2021.11.12.21266273: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Participant recruitment and study design: Pregnant individuals at two tertiary care centers were approached for enrollment in the COVID-19 pregnancy biorepository study between January 2021 and September 2021, Protocol #2020P003538, approved by Mass General Brigham Institutional Review Board (IRB).
    Consent: Eligible participants were pregnant, greater than or equal to 18 years old, able to provide informed consent, and receiving the Ad26.COV2.S, mRNA-1273, or BNT162b2 COVID-19 vaccine during pregnancy.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Bead-based functional assays: For antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP) and antibody-dependent complement deposition (ADCD), D614G Spike was biotinylated using Sulfo-NHS-LC-LC biotin (Thermo Fisher Scientific) and desalted using Zeba Columns (Thermo Fisher Scientific)
    antibody-dependent neutrophil phagocytosis ( ADNP
    suggested: None
    antibody-dependent complement deposition ( ADCD)
    suggested: None
    Sulfo-NHS-LC-LC biotin
    suggested: None
    Multiplexed Luminex Assay: A multiplexed Luminex assay was used to determine the relative concentration of antigen-specific antibody isotype and subclass titer and Fc receptor binding.
    antigen-specific antibody isotype and subclass titer and Fc receptor binding .
    suggested: None
    Antigen-specific antibody isotypes were measured using PE-coupled mouse anti-human antibodies (Southern Biotech) specific for each specific isotype.
    Antigen-specific
    suggested: None
    anti-human antibodies
    suggested: None
    Plates were washed, and a horseradish peroxidase (HRP)-conjugated goat anti-human IgG antibody (Bethyl Laboratories) was added for detection of Spike-specific IgG.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For ADCP, THP-1 cells (ATCC) were added to plates at a concentration of 2.5×104 cells/mL.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: For univariate analysis, statistics were calculated using GraphPad Prism version 8.0.
    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 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.

  5. Version published to 10.1101/2021.11.12.21266273v1 on medRxiv