Departamento de Fisiología, Biología Molecular y Celular, Instituto de Biociencias, Biotecnología y Biología Traslacional (IB3) e Instituto de Química Biológica (IQUIBICEN), FCEN, UBA, CONICET, Buenos Aires, CABA, Argentina.
Escuela Superior de Medicina, Universidad Nacional Mar del Plata-Hospital Interzonal Especializado Materno Infantil Don Vitorio Tetamanti, Mar del Plata, Buenos Aires, Argentina.
J Clin Immunol. 2023 Feb;43(2):271-285. doi: 10.1007/s10875-022-01382-7. Epub 2022 Oct 17.
Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n = 118) and age-matched healthy controls (HC) (n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry.No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC (p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection.In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease.
阿根廷的先天性免疫缺陷（IEI）患者被鼓励接种许可的 Sputnik、AstraZeneca、Sinopharm、Moderna 和 Pfizer 疫苗，尽管大多数关于现有疫苗体液和细胞反应组合的数据都来自于在健康个体中进行的试验。我们旨在评估不同疫苗在阿根廷 IEI 患者中的安全性和免疫原性。研究队列包括成年和儿科 IEI 患者（n=118）和年龄匹配的健康对照（HC）（n=37）。通过 ELISA 测量 IgG 抗刺突/受体结合域（S/RBD）和抗核衣壳（N）抗体来评估 B 细胞反应。还通过 alpha-S 蛋白表达的假病毒测定评估中和抗体。T 细胞反应通过 IFN-γ在 S 或 N 刺激的 PBMC 上的分泌通过 ELISPOT 进行分析，通过流式细胞术评估 S 特异性循环滤泡辅助 T 细胞（TFH）的频率。未观察到与疫苗相关的中度/重度不良事件。儿科和成年 IEI 患者的抗 S/RBD 滴度与年龄匹配的 HC 队列相比均有显著差异（p<0.05）。与年龄匹配的 HC 相比，患者队列中的中和抗体也明显较低（p<0.01）。84.5%的 IEI 患者出现 S 特异性 IFN-γ反应，82.1%的患者出现 S 特异性 TFH 细胞。主要在儿科人群中使用的 Moderna 疫苗在 IEI 患者中引起更强的体液反应，无论是抗体滴度还是中和能力，但疫苗平台之间的细胞免疫反应相似。未观察到已接种和未感染过 SARS-CoV-2 的患者之间的体液反应存在差异。总之，COVID-19 疫苗在 IEI 患者中表现出安全性，尽管免疫原性低于 HC，但它们显示出特异性抗 S/RBD IgG、中和抗体滴度和 IFN-γ分泌细胞的 T 细胞依赖性细胞免疫。这些发现可能为 IEI 患者推荐使用所有可用疫苗进行疫苗接种以预防 COVID-19 疾病提供指导。
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