Comprehensive antibody profiling of mRNA vaccination in children

  1. Yannic C Bartsch
  2. Kerri J St Denis
  3. Paulina Kaplonek
  4. Jaewon Kang
  5. Evan C. Lam
  6. Madeleine D Burns
  7. Eva J Farkas
  8. Jameson P Davis
  9. Brittany P Boribong
  10. Andrea G Edlow
  11. Alessio Fasano
  12. Wayne Shreffler
  13. Dace Zavadska
  14. Marina Johnson
  15. David Goldblatt
  16. Alejandro B Balazs
  17. Lael M Yonker
  18. Galit Alter

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Abstract

While children have been largely spared from COVID-19 disease, the emergence of viral variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Given the recent announcement of incomplete immunity induced by the pediatric dose of the BNT162b2 vaccine in young children, here we aimed to deeply profile and compare the vaccine-induced humoral immune response in 6-11 year old children receiving the pediatric (50μg) or adult (100μg) dose of the mRNA-1273 vaccine compared to adults and naturally infected children or children that experienced multi inflammatory syndrome in children (MIS-C) for the first time. Children elicited an IgG dominant vaccine induced immune response, surpassing adults at a matched 100μg dose, but more variable immunity at a 50μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron receptor binding domain-binding, but robustly preserved omicron Spike-receptor binding, with robustly preserved Fc-receptor binding capabilities, in a dose dependent manner. These data indicate that while both 50μg and 100μg of mRNA vaccination in children elicits robust cross-VOC antibody responses, 100ug of mRNA in children results in highly preserved omicron-specific functional humoral immunity.

One-Sentence Summary

mRNA vaccination elicits robust humoral immune responses to SARS-CoV-2 in children 6-11 years of age.

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  3. Version published to 10.1101/2021.10.07.463592v2 on bioRxiv
  4. ScreenIT

    SciScore for 10.1101/2021.10.07.463592: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All pediatric participants provided informed assent and their legal guardian provided informed consent prior to participation in the observational MGH Pediatric COVID-19 Biorepository.
    IRB: This study was overseen and approved by the MassGeneral Institutional Review Board (IRB #2020P00955)
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody isotype and Fc receptor binding: Antigen-specific antibody isotype and subclass titers and Fc receptor binding profiles were analyzed with a custom multiplex Luminex assay as described previously (29).
    Antigen-specific
    suggested: None
    Coupled beads were incubated with diluted plasma samples washed, and Ig isotypes or subclasses with a 1:100 diluted PE-conjugated secondary antibody for IgG1 (clone: HP6001), IgG2 (clone: 31-7-4), IgG3 (clone: HP6050), IgG4 (clone: HP6025), IgM (clone: SA-DA4), IgA1 (clone: B3506B4) or IgA2 (clone: A9604D2) (all Southern Biotech, AL, USA), respectively.
    IgG1
    suggested: None
    IgG2
    suggested: None
    IgG3
    suggested: None
    IgG4
    suggested: None
    IgA1
    suggested: None
    IgA2
    suggested: None
    EDTA containing PBS (15mM) was used to stop the complement reaction and deposited C3 on beads was stained with anti-guinea pig C3-FITC antibody (MP Biomedicals, CA, USA, 1:100
    anti-guinea pig C3-FITC
    suggested: None
    Antibody-Dependent-Neutrophil-Phagocytosis (
    Antibody-Dependent-Neutrophil-Phagocytosis
    suggested: None
    Antibody-Dependent-THP-1 Cell-Phagocytosis (ADCP):
    Antibody-Dependent-THP-1 Cell-Phagocytosis ( ADCP)
    suggested: None
    Antibody-Dependent-NK-Activation (ADNKA): To determine Antibody-dependent NK cell activation, MaxiSporp ELISA plates (Thermo Fisher) were coated with respective antigen for 2h at RT and then blocked with 5% BSA (Sigma-Aldrich).
    Antibody-Dependent-NK-Activation
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus neutralization: Three-fold serial dilutions ranging from 1:12 to 1:8748 were performed for each plasma sample before adding 50–250 infectious units of pseudovirus expressing the SARS-CoV-2 reference (Wuhan/wildtype) or delta variant Spike to hACE-2 expressing HEK293 cells for 1 hour.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Software and Algorithms
    SentencesResources
    Data analysis and Statistics: Data analysis was performed using GraphPad Prism (v.9.2.0) and RStudio (v.1.3 and R v.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    Heatmap was generated using the pheatmap package (v.1.0.12) in R using Z-scored values.
    pheatmap
    suggested: (pheatmap, RRID:SCR_016418)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04796896RecruitingA Study to Evaluate Safety and Effectiveness of mRNA-1273 CO…
    NCT04283461Active, not recruitingSafety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1…

    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 10.1101/2021.10.07.463592v1 on bioRxiv