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  • Clinical Research Article
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Immunogenicity of COVID-19 booster vaccines in children receiving immunosuppressive medications

Pediatric Research (2025)Cite this article

Abstract

Background

As many jurisdictions move towards seasonal COVID-19 vaccines, there remains insufficient data on optimal vaccination strategies for children with immune-mediated inflammatory diseases (IMID) treated with immunomodulatory therapies.

Methods

A prospective observational cohort study was performed, with clinical data and biosamples longitudinally collected to determine the effect of immunomodulatory therapies on the antibody response to four COVID-19 vaccine doses. Antibodies against the SARS-CoV-2 spike, receptor-binding domain, and nucleocapsid proteins were measured.

Results

Following doses two and three, antibody responses were lowest in participants treated with biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), of which TNF inhibitors were the most common. Rates of antibody decay were similar between treatment groups, but weaker initial responses in the b/tsDMARD group led to antibody levels dipping to low values within four months of vaccination. The fourth vaccine dose significantly boosted antibody levels in the b/tsDMARD group, resulting in a sustained response. Among additional samples collected from children with hybrid immunity (i.e., vaccinated and prior SARS-CoV-2 infection), no differences in antibody levels were found between participants who were or were not treated with b/tsDMARDs.

Conclusions

These data support providers in counselling families regarding the importance of annual COVID-19 booster vaccines in children with IMID.

Impact

  • There is conflicting evidence on the effect of immunosuppressive treatments on the antibody response to vaccination in paediatric populations.

  • Long-term follow-up of children treated with various immunosuppressive therapies as they received booster COVID-19 vaccines demonstrated that antibody responses to the second and third vaccine dose were impaired in children treated with biologics (mainly TNF inhibitors).

  • Deficits in the antibody response were largely corrected by a fourth vaccine dose or infection with SARS-CoV-2.

  • Children treated with biologic therapies require a full suite of COVID-19 vaccines and should be strongly encouraged to receive seasonal COVID-19 vaccine boosters.

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Fig. 1: Case vignettes.
Fig. 2: Effect of treatment on the magnitude of the antibody response.
Fig. 3: Sensitivity analyses of the effect of treatment on the magnitude of the antibody response.
Fig. 4: Effect of treatment on the kinetics of the antibody response following vaccination.
Fig. 5: Effect of infection on the antibody response following dose three.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Geneviève Mailhot, Melanie Delgado-Brand, Tulunay Tursun, Martina Tersigni, Roya M. Dayam, and Freda Qi for their role in SARS-CoV-2 serology analysis, which was conducted using robotic equipment in the Network Biology Collaborative Centre High-Throughput Screening Facility (RRID: SCR_025390), a facility supported by the Canada Foundation for Innovation and the Ontario Government. Antigens, protein standards, and secondary antibodies for serum ELISA were kindly provided by the Pandemic Response Challenge Program of the National Research Council of Canada (Dr. Yves Durocher).

Funding

This project was supported by funding from the Government of Canada, through the COVID-19 Immunity Task Force. JRS was supported by a fellowship from the Canadian Immunization Research Network. RSMY was supported by the Hak Ming and Deborah Chiu Chair in Paediatric Translational Research from the Hospital for Sick Children, University of Toronto. ACG is the Canada Research Chair in Functional Proteomics and the Sinai 100 Louis Siminovitch Chair in Research. SMB was supported by the Cenovus Energy Chair and the ACHF Chair for Pediatric Research from the Alberta Children’s Hospital Foundation and the University of Calgary. EIB holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. LH holds a Canada Research Chair in Genetics of Rare Systemic Inflammatory Diseases.

Author information

Authors and Affiliations

  1. Center for Vaccine Preventable Diseases, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Janna R. Shapiro

  2. Department of Immunology, University of Toronto, Toronto, ON, Canada

    Janna R. Shapiro & Rae SM Yeung

  3. Division of Rheumatology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Florence Choi & Rae SM Yeung

  4. Cell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada

    Amy Xu, Trang T. Duong & Rae SM Yeung

  5. Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Sinai Health, Toronto, ON, Canada

    Anne-Claude Gingras & Karen Colwill

  6. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Anne-Claude Gingras

  7. Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montreal, QC, Canada

    Sasha Bernatsky

  8. Division of Rheumatology, McGill University Health Centre, Montreal, QC, Canada

    Sasha Bernatsky

  9. Division of Rheumatology, Department of Paediatrics, Alberta Children’s Hospital, Cumming School of Medicine, University of Calgary, Calgary, AL, Canada

    Susanne M. Benseler

  10. Children’s Health, Ireland, Dublin, Ireland

    Susanne M. Benseler

  11. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada

    Eric I. Benchimol & Peter C. Church

  12. Division of Rheumatology, Janeway Children’s Hospital & Rehabilitation Centre, Saint John’s, NL, Canada

    Paul Dancey

  13. SickKids Research Institute, Peter Gilgan Centre for Research & Learning, Toronto, ON, Canada

    Dilan Dissanayake

  14. Division of Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada

    Linda Hiraki, Andrea Knight, Deborah Levy, Elizaveta Limenis, Lynn Spiegel & Shirley Tse

  15. Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Kristin Houghton

  16. Division of Pediatric Rheumatology, Dalhousie University, Halifax, NS, Canada

    Adam Huber

  17. Division of Pediatric Rheumatology, Department of Pediatrics, Jim Pattison Children’s Hospital, University of Saskatchewan, Saskatoon, SK, Canada

    Mehul Jariwala

  18. Department of Pediatrics, Division of Rheumatology, University of Alberta, Edmonton, AB, Canada

    Tara McGrath

  19. Division of Rheumatology, Department of Pediatrics, McGill University, Montreal, QC, Canada

    Rosie Scuccimarri

  20. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Ruud H. J. Verstegen

Authors
  1. Janna R. Shapiro
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  2. Florence Choi
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  3. Amy Xu
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  4. Trang T. Duong
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  5. Anne-Claude Gingras
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  6. Karen Colwill
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  7. Sasha Bernatsky
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  8. Susanne M. Benseler
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  9. Rae SM Yeung
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Consortia

on behalf of the SUCCEED KIDS Team

  • Eric I. Benchimol
  • , Peter C. Church
  • , Paul Dancey
  • , Dilan Dissanayake
  • , Linda Hiraki
  • , Kristin Houghton
  • , Adam Huber
  • , Mehul Jariwala
  • , Andrea Knight
  • , Deborah Levy
  • , Elizaveta Limenis
  • , Tara McGrath
  • , Rosie Scuccimarri
  • , Lynn Spiegel
  • , Shirley Tse
  •  & Ruud H. J. Verstegen

Contributions

R.S.M.Y. oversaw all aspects of the study. R.S.M.Y., S.B. and S.B. conceptualized the study and acquired funding. A.X. and T.D. were responsible in project administration, data collection, and sample processing. The members of the SUCCEED Kids study team recruited participants and collected data. A.C.G. and K.C. performed and oversaw the serology testing. J.R.S., F.C. and A.X. curated data. JRS performed formal data analysis, created figures, and drafted the manuscript. All authors reviewed the manuscript and provided editorial contributions.

Corresponding author

Correspondence to Rae SM Yeung.

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The authors declare no competing interests.

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Shapiro, J.R., Choi, F., Xu, A. et al. Immunogenicity of COVID-19 booster vaccines in children receiving immunosuppressive medications. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04174-y

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  • DOI: https://doi.org/10.1038/s41390-025-04174-y

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