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

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). 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. 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. 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.