Lopes da Silva Vitor Gabriel, Schmitz Gabriela Justamante Händel, Sullivan Kathleen E, Barbate Júlia, de Haro Azinar Maria Izabel, Aranda Carolina Sanchez, de Moraes-Pinto Maria Isabel
Departamento de Pediatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Departamento de Clínica Médica, Universidade de São Paulo, São Paulo, SP, Brazil.
Front Immunol. 2025 Mar 6;16:1538453. doi: 10.3389/fimmu.2025.1538453. eCollection 2025.
Patients with Inborn Errors of Immunity (IEI) are at higher risk of severe SARS-CoV-2 infection. We evaluated humoral and cellular responses to COVID-19 vaccines in Brazilian patients with IEI and healthy controls.
Fifty-five patients with IEI (13-61 years) and 60 controls (13-71 years) received inactivated SARS-CoV-2 (CoronaVac), non-replicating virus-vectored (ChAdOx1 nCoV-19, AstraZeneca) or monovalent mRNA (Original strain of BNT162b2, Pfizer-BioNTech) and bivalent mRNA (Original/Omicron BA.1, Pfizer-BioNTech) vaccines and were sampled five times. Diagnoses included common variable immunodeficiency (n=25), specific antibody deficiency (n=9), ataxia-telangiectasia (n=5), X-linked agammaglobulinemia (n=4), PIK3CD-related disorders (n=4), hyper-IgM syndrome (n=4), combined immunodeficiency (n=3), and STAT1 gain-of-function (n=1). Humoral immunity was assessed via multiplex microarray for Spike, Nucleocapsid, RBD-Wuhan, RBD-Delta, RBD-BA.1, RBD-BA.2 and RBD-BA.5 neutralizing antibodies. T-cell responses to Spike and Nucleocapsid were assessed using ELISpot.
Patients with IEI exhibited significantly lower levels of Nucleocapsid and RBD-neutralizing antibodies (p < 0.05). Notable differences in RBD-BA.2 (p = 0.008) and IgG-Nucleocapsid (p = 0.010) levels emerged over time. T-cell responses to Spike were stronger in patients with IEI post-booster (405 vs. 149 spot-forming cells/million PBMC; p = 0.002). Both groups showed enhanced Nucleocapsid-specific cellular responses over time (p = 0.017). COVID-19 hospitalization rates among patients with IEI with SARS-CoV-2 diagnosis dropped from 33.3% to zero after the first booster dose.
While humoral responses to SARS-CoV-2 vaccines were weaker in patients with IEI, their cellular immunity was similar to controls. Boosters enhanced both humoral and cellular responses. After completion of the vaccination protocol, none of the patients with IEI were hospitalized with COVID-19. Robust T-cell responses may play a critical role in protecting patients with IEI from severe COVID-19 and mortality.
先天性免疫缺陷（IEI）患者感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的风险更高。我们评估了巴西IEI患者和健康对照者对新冠疫苗的体液和细胞免疫反应。
55例IEI患者（13 - 61岁）和60例对照者（13 - 71岁）接种了灭活SARS-CoV-2疫苗（科兴新冠疫苗）、非复制型病毒载体疫苗（ChAdOx1 nCoV-19，阿斯利康）或单价mRNA疫苗（BNT162b2原始毒株，辉瑞 - 生物科技）以及二价mRNA疫苗（原始毒株/奥密克戎BA.1，辉瑞 - 生物科技），并进行了5次采样。诊断包括常见变异型免疫缺陷（n = 25）、特异性抗体缺陷（n = 9）、共济失调 - 毛细血管扩张症（n = 5）、X连锁无丙种球蛋白血症（n = 4）、PIK3CD相关疾病（n = 4）、高IgM综合征（n = 4）、联合免疫缺陷（n = 3）和STAT1功能获得性突变（n = 1）。通过多重微阵列检测针对刺突蛋白、核衣壳蛋白、武汉株RBD、德尔塔株RBD、奥密克戎BA.1株RBD、奥密克戎BA.2株RBD和奥密克戎BA.5株RBD的中和抗体来评估体液免疫。使用酶联免疫斑点法（ELISpot）评估对刺突蛋白和核衣壳蛋白的T细胞反应。
IEI患者的核衣壳蛋白和RBD中和抗体水平显著较低（p < 0.05）。随着时间推移，RBD - BA.2（p = 0.008）和IgG - 核衣壳蛋白（p = 0.010）水平出现显著差异。加强免疫后，IEI患者对刺突蛋白的T细胞反应更强（405个与149个斑点形成细胞/百万外周血单个核细胞；p = 0.002）。两组的核衣壳蛋白特异性细胞反应均随时间增强（p = 0.017）。确诊感染SARS-CoV-2的IEI患者中，首次加强免疫后新冠住院率从33.3%降至零。
虽然IEI患者对SARS-CoV-2疫苗的体液免疫反应较弱，但其细胞免疫与对照者相似。加强免疫增强了体液和细胞免疫反应。完成疫苗接种方案后，没有IEI患者因新冠住院。强大的T细胞反应可能在保护IEI患者免受严重新冠感染和死亡方面发挥关键作用。
