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Purpose <p>To assess the durability of SARS-CoV-2-specific immunity following three doses of COVID-19 vaccine in children with inborn errors of immunity (IEI).</p> Methods <p>In this multi-center observational study, we compared SARS-CoV-2 specific humoral and T-cell immunity 24&#xa0;weeks after the third dose of monovalent mRNA COVID-19 vaccine in children (5–18&#xa0;years) with IEI and healthy controls (HC). Participants with IEI were categorized into predominant antibody deficiency (PAD) or non-PAD subgroups.</p> Results <p>Forty-three children with IEI (26 with PAD and 17 with non-PAD; 16 females, mean age 10.5 ± 4&#xa0;years) and 12 HC (7 females, mean age 14.1 ± 3&#xa0;years) were included. Anti-RBD IgG and anti-S IgG seropositivity was 100% in both groups. However, geometric mean concentrations (95% confidence interval) were significantly lower in IEI versus HC: 1,349.0 (905.4–2,009.9) vs. 3,324.2 (1,762.8–6,268.6) BAU/mL, <i>p</i> = 0.03 for anti-RBD IgG, and 1,336.4 (938.2 – 1,903.5) vs. 3,320.9 (2,158.4 – 5109.7), BAU/mL, <i>p</i> = 0.012 for anti-S IgG. Neutralizing antibody titers against ancestral and Omicron BA.1, BA.4/BA.5, and XBB.1.5 were also significantly lower in IEI, especially among PAD participants (<i>p</i> = 0.001). In contrast, S-specific T-cell responses did not differ significantly between IEI and HC.</p> Conclusion <p>Six months after the third COVID-19 vaccine dose, children with IEI retained SARS-CoV-2-specific humoral and cellular immunity, though antibody responses were attenuated, particularly among PAD cases. Importantly, spike-specific T-cell responses were preserved and comparable to HC. These findings underscore that, in real-world settings, children with IEI maintain durable SARS-CoV-2-specific cellular immunity—including memory T-cell responses—highlighting the benefit of vaccination and the potential for continued immune protection despite impaired humoral responses.</p>

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Three Doses and Six Months Later: Real-World SARS-CoV-2 Specific Humoral and Cell-Mediated Immunity in Children With Inborn Errors of Immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月25日

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  • Luana L. T. N. Porto,
  • Dina Yazji,
  • Dana Unninayar,
  • Hélène Decaluwe,
  • Beata Derfalvi,
  • Alejandro Palma,
  • Thomas Issekutz,
  • Tatiana Kalashnikova,
  • Luis Murguía-Favela,
  • Anne Pham-Huy,
  • Tamar Rubin,
  • Sneha Suresh,
  • Julia Upton,
  • Nicola A. M. Wright,
  • Hugo Chapdelaine,
  • Emilia Liana Falcone,
  • Karina A. Top,
  • Manish Sadarangani,
  • Donald C. Vinh,
  • Lisa Barrett,
  • Sharon Oldford,
  • Marc-Andre Langlois,
  • Corey Arnold,
  • Tinghua Zhang,
  • Tim Ramsay,
  • Juthaporn Cowan,
  • Bruce Ritchie,
  • Arianne C. Buchan,
  • Chrystyna Kalincinsky,
  • Elie Haddad,
  • Fabien Touzot,
  • Gina Lacuesta,
  • Kyla Hildebrand,
  • Vy Kim,
  • Stephen D. Betschel

摘要

Purpose

To assess the durability of SARS-CoV-2-specific immunity following three doses of COVID-19 vaccine in children with inborn errors of immunity (IEI).

Methods

In this multi-center observational study, we compared SARS-CoV-2 specific humoral and T-cell immunity 24 weeks after the third dose of monovalent mRNA COVID-19 vaccine in children (5–18 years) with IEI and healthy controls (HC). Participants with IEI were categorized into predominant antibody deficiency (PAD) or non-PAD subgroups.

Results

Forty-three children with IEI (26 with PAD and 17 with non-PAD; 16 females, mean age 10.5 ± 4 years) and 12 HC (7 females, mean age 14.1 ± 3 years) were included. Anti-RBD IgG and anti-S IgG seropositivity was 100% in both groups. However, geometric mean concentrations (95% confidence interval) were significantly lower in IEI versus HC: 1,349.0 (905.4–2,009.9) vs. 3,324.2 (1,762.8–6,268.6) BAU/mL, p = 0.03 for anti-RBD IgG, and 1,336.4 (938.2 – 1,903.5) vs. 3,320.9 (2,158.4 – 5109.7), BAU/mL, p = 0.012 for anti-S IgG. Neutralizing antibody titers against ancestral and Omicron BA.1, BA.4/BA.5, and XBB.1.5 were also significantly lower in IEI, especially among PAD participants (p = 0.001). In contrast, S-specific T-cell responses did not differ significantly between IEI and HC.

Conclusion

Six months after the third COVID-19 vaccine dose, children with IEI retained SARS-CoV-2-specific humoral and cellular immunity, though antibody responses were attenuated, particularly among PAD cases. Importantly, spike-specific T-cell responses were preserved and comparable to HC. These findings underscore that, in real-world settings, children with IEI maintain durable SARS-CoV-2-specific cellular immunity—including memory T-cell responses—highlighting the benefit of vaccination and the potential for continued immune protection despite impaired humoral responses.