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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	114873
Number of pages	12
Journal	The Journal of pediatrics
Volume	289
Early online date	24 Oct 2025
DOIs	https://doi.org/10.1016/j.jpeds.2025.114873
Publication status	Published - Feb 2026

Bibliographical note

Abbreviations
CTCTU, Cancer Research UK Clinical Trials Unit; CYP, Children and young people; POST, Post solid organ transplant; RIC, Rheumatologic inflammatory conditions

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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Cite this

Brugha, R., Kirkham, A., Bate, J., Burke, G. A. A., Hughes, A., Magwaro, S., Pope, A. M., Beesley, R., Lax, S., Kelly, E., Greenland, M., Minassian, A. M., Liu, X., Billingham, L., McInnes, I., Goodyear, C. S., Kearns, P., Wedderburn, L. R., & OCTAVE-Minor Collaborative Group (2026). SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study. The Journal of pediatrics, 289, Article 114873. https://doi.org/10.1016/j.jpeds.2025.114873

@article{00f56187f20141ccaf0bfce3abfcba18,

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

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 = "children and adolescents, clinical trial, COVID-19, immunosuppressed patients, OCTAVE-Minor, SARS-CoV-2, vaccine strategy",

author = "Rossa Brugha and Amanda Kirkham and Jessica Bate and Burke, \{G.A. Amos\} and Ana Hughes and Sophia Magwaro and Pope, \{Ann M.\} and Richard Beesley and Si{\^a}n Lax and Eimear Kelly and Melanie Greenland and Minassian, \{Angela M.\} and Xinxue Liu and Lucinda Billingham and Iain McInnes and Goodyear, \{Carl S.\} and Pamela Kearns and Wedderburn, \{Lucy R.\} and \{OCTAVE-Minor Collaborative Group\}",

note = "Abbreviations CTCTU, Cancer Research UK Clinical Trials Unit; CYP, Children and young people; POST, Post solid organ transplant; RIC, Rheumatologic inflammatory conditions",

year = "2026",

month = feb,

doi = "10.1016/j.jpeds.2025.114873",

language = "English",

volume = "289",

journal = "The Journal of pediatrics",

issn = "0022-3476",

publisher = "Elsevier",

}

Brugha, R, Kirkham, A, Bate, J, Burke, GAA, Hughes, A, Magwaro, S, Pope, AM, Beesley, R, Lax, S, Kelly, E, Greenland, M, Minassian, AM, Liu, X, Billingham, L, McInnes, I, Goodyear, CS, Kearns, P, Wedderburn, LR & OCTAVE-Minor Collaborative Group 2026, 'SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study', The Journal of pediatrics, vol. 289, 114873. https://doi.org/10.1016/j.jpeds.2025.114873

TY - JOUR

T1 - SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems

T2 - A Prospective, Observational Study

AU - Brugha, Rossa

AU - Kirkham, Amanda

AU - Bate, Jessica

AU - Burke, G.A. Amos

AU - Hughes, Ana

AU - Magwaro, Sophia

AU - Pope, Ann M.

AU - Beesley, Richard

AU - Lax, Siân

AU - Kelly, Eimear

AU - Greenland, Melanie

AU - Minassian, Angela M.

AU - Liu, Xinxue

AU - Billingham, Lucinda

AU - McInnes, Iain

AU - Goodyear, Carl S.

AU - Kearns, Pamela

AU - Wedderburn, Lucy R.

AU - OCTAVE-Minor Collaborative Group

N1 - Abbreviations CTCTU, Cancer Research UK Clinical Trials Unit; CYP, Children and young people; POST, Post solid organ transplant; RIC, Rheumatologic inflammatory conditions

PY - 2026/2

Y1 - 2026/2

N2 - 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.

AB - 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.

KW - children and adolescents

KW - clinical trial

KW - COVID-19

KW - immunosuppressed patients

KW - OCTAVE-Minor

KW - SARS-CoV-2

KW - vaccine strategy

U2 - 10.1016/j.jpeds.2025.114873

DO - 10.1016/j.jpeds.2025.114873

M3 - Article

SN - 0022-3476

VL - 289

JO - The Journal of pediatrics

JF - The Journal of pediatrics

M1 - 114873

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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