SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study

Rossa Brugha; Amanda Kirkham; Jessica Bate; G A Amos Burke; Ana Hughes; Sophia Magwaro; Ann M Pope; Richard Beesley; Siân Lax; Eimear Kelly; Melanie Greenland; Angela M Minassian; Xinxue Liu; Lucinda Billingham; Iain McInnes; Carl S Goodyear; Pamela Kearns; Lucy R Wedderburn; OCTAVE-Minor Collaborative Group

doi:10.1016/j.jpeds.2025.114873

SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study

J Pediatr. 2025 Oct 24:289:114873. doi: 10.1016/j.jpeds.2025.114873. Online ahead of print.

Authors

Rossa Brugha¹, Amanda Kirkham², Jessica Bate³, G A Amos Burke⁴, Ana Hughes², Sophia Magwaro², Ann M Pope², Richard Beesley⁵, Siân Lax², Eimear Kelly⁶, Melanie Greenland⁶, Angela M Minassian⁷, Xinxue Liu⁶, Lucinda Billingham², Iain McInnes⁸, Carl S Goodyear⁸, Pamela Kearns², Lucy R Wedderburn⁹; OCTAVE-Minor Collaborative Group

Affiliations

¹ Cardiothoracic Transplantation, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom; National Institute for Health Research (NIHR) GOSH Biomedical Research Centre, London, United Kingdom. Electronic address: rossa.brugha@gosh.nhs.uk.
² Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham Edgbaston, Birmingham, United Kingdom.
³ Department of Pediatric Oncology, University Hospitals Southampton NHS Foundation Trust, Southampton, United Kingdom.
⁴ Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham Edgbaston, Birmingham, United Kingdom; Department of Pediatric Oncology and Hematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
⁵ Patient Representative for the OCTAVE Study, Juvenile Arthritis Research, Tonbridge, United Kingdom.
⁶ Department of Pediatrics, Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
⁷ Department of Pediatrics, Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom; Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
⁸ College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
⁹ National Institute for Health Research (NIHR) GOSH Biomedical Research Centre, London, United Kingdom; Pediatric Rheumatology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom; Infection, Immunity and Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.

PMID: 41139014
DOI: 10.1016/j.jpeds.2025.114873

Abstract

Objective: To investigate the concern that children and young people (CYP) receiving immune-suppressing treatments mount impaired responses to vaccines, in CYP compared with healthy controls.

Study design: We prospectively enrolled CYP aged 5-17 years who are receiving we measured humoral and cellular biological response-modifying therapies for rheumatologic inflammatory conditions (RICs), or post solid organ transplant (PSOT), or cancer chemotherapy before and/or after routine vaccinations with BNT162b2 vaccine. Responses to SARS-CoV-2 vaccination were assessed by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics) and T-cell responses (Oxford Immunotec). Response to wild-type and SARS-CoV-2 variants (BA5, XBB1.5) was assessed by microneutralization assay. Control data were from ComCOV3.

Results: We enrolled 125 eligible participants (RIC n = 54 [43.2%], PSOT n = 49 [39.2%], cancer n = 22 [17.6%]); 58 (46.4%) female; mean age, 12.9 ± 2.9 years. Seventy-nine participants (63.2%) had prior COVID-19 and 28 (22.4%) were unvaccinated before the study; 97 participants (77.6%) received ≥1 vaccines; 13 (10.4%) reported COVID-19 infection during follow-up. CYP receiving chemotherapy for cancer had lower antibody responses post vaccine: anti-SARS-CoV-2 spike antibodies (median, 26.7 AU/mL; IQR, 2.3-1088.0 AU/mL) compared with RIC (median, 6970.0 AU/mL; IQR, 1417.0-18163.0 AU/mL) and PSOT (medina, 7899.0 AU/mL; IQR, 1711.0-19201.0 AU/mL) (both P < .0001). T-cell responses were also reduced in the cancer group (median, 8.0 SFC/10⁶ PBMCs; IQR, 0.0-48.0 SFC/10⁶ PBMCs) compared with RIC (median, 110.0 SFC/10⁶ PBMCs; IQR, 44.0-260.0 SFC/10⁶ PBMCs; P = .009) and PSOT (median, 74.0 SFC/10⁶ PBMCs; IQR, 32.0-160.0 SFC/10⁶ PBMCs; P = .003).

Conclusions: Children receiving immune-suppressing therapies for RIC and PSOT had antibody and T-cell responses after the third vaccine dose that approached levels reported in healthy controls. Children who were receiving cancer chemotherapy, however, showed substantially reduced humoral and T-cell responses.

Trial registration: ISRCTN 12821688; https://www.isrctn.com/ISRCTN12821688.

Keywords: COVID-19; OCTAVE-Minor; SARS-CoV-2; children and adolescents; clinical trial; immunosuppressed patients; vaccine strategy.