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SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A
Rossa Brugha1, Amanda Kirkham2, Jessica Bate3
1Cardiothoracic Transplantation, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom; National Institute for Health Research (NIHR) GOSH Biomedical Research Centre, London, United Kingdom.
Insights
Children on immunosuppressants for rheumatologic conditions and organ transplants showed good vaccine responses. However, children undergoing cancer chemotherapy had significantly impaired antibody and T-cell responses to COVID-19 vaccines.
Area of Science:
- Immunology
- Pediatric Oncology
- Vaccinology
Background:
- Children and young people (CYP) on immunosuppressive therapies may have reduced vaccine responses.
- Assessing vaccine immunogenicity in pediatric populations undergoing treatment is crucial for public health.
Purpose of the Study:
- To compare humoral and cellular immune responses to BNT162b2 vaccination in CYP with rheumatologic inflammatory conditions (RICs), post solid organ transplant (PSOT), or cancer chemotherapy against healthy controls.
- To investigate the impact of specific immunosuppressive treatments on vaccine efficacy in pediatric patients.
Main Methods:
- Prospective enrollment of 125 CYP (aged 5-17) receiving therapies for RIC, PSOT, or cancer.
- Measurement of anti-SARS-CoV-2 spike antibodies and T-cell responses post-BNT162b2 vaccination.
- Assessment of antibody neutralization against wild-type and SARS-CoV-2 variants (BA5, XBB1.5).
Main Results:
- CYP with RIC and PSOT demonstrated antibody and T-cell responses approaching those of healthy controls.
- CYP receiving cancer chemotherapy exhibited significantly lower antibody responses (P < .0001) compared to RIC and PSOT groups.
- Reduced T-cell responses were observed in the cancer group (P = .009 and P = .003) versus RIC and PSOT groups, respectively.
Conclusions:
- Pediatric patients with RIC and PSOT achieve robust immune responses post-vaccination, similar to healthy individuals.
- Cancer chemotherapy in CYP substantially impairs humoral and cellular immune responses to COVID-19 vaccines.
- Findings highlight the need for tailored vaccination strategies and monitoring in pediatric cancer patients.
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.
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