Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Comprehensive Center for Infection Medicine, Medical University of Vienna, Austria (CCIM), Vienna, Austria.
Wien Klin Wochenschr. 2024 Nov;136(21-22):598-607. doi: 10.1007/s00508-024-02459-6. Epub 2024 Oct 24.
Impaired immune response to COVID-19 (coronavirus disease 2019) vaccination has been reported in patients with inborn errors of immunity (IEI). Repetitive vaccinations are recommended for this vulnerable group. Due to the high diversity within IEI patients, additional safety and immunogenicity data are needed to better understand these aspects especially in less common immunodeficiency syndromes. In this prospective open-label clinical trial, we assessed the humoral immune response and the T‑cell response in patients with IEI or severe MBL (mannose-binding lectin) deficiency (IEI/MBLdef) after three vaccinations. A total of 16 patients and 16 matched healthy controls (HC) with suboptimal humoral response defined by anti-SARS-CoV‑2 RBD (severe acute respiratory syndrome coronavirus type 2 receptor binding domain) antibodies below 1500 BAU/ml (binding antibody units per ml) after the second COVID-19 vaccination were enrolled in this study and qualified for a third mRNA vaccine dose. After 4 weeks following vaccination, 100% of HC and 75% of IEI/MBLdef patients exhibited anti-SARS-CoV‑2 RBD antibodies > 1500 BAU/ml, although the difference was not statistically significant (75% vs. 100%; p = 0.109). Although post-vaccination IEI/MBLdef patients demonstrated significantly increased anti-SARS-CoV‑2 RBD antibodies and neutralizing antibodies compared to baseline, these responses were significantly lower in IEI/MBLdef patients compared to HCs. Notably, the third vaccination augmented the cellular immune response to both wild-type and omicron peptide stimulation. No serious adverse events were reported within the 4‑week follow-up period and, importantly, vaccination had little to no effect on the long-term disease activity and fatigue. This trial strongly supports the recommendation of repeated COVID-19 vaccinations for patients suffering from immunodeficiencies, especially when they exhibit an initially limited response to the vaccine.
免疫缺陷患者（先天性免疫缺陷或严重 MBL 缺乏）对 COVID-19（新型冠状病毒病 2019）疫苗的免疫反应受损已有报道。该脆弱群体需要进行重复接种。由于免疫缺陷患者的多样性较高，需要额外的安全性和免疫原性数据来更好地了解这些方面，尤其是在不太常见的免疫缺陷综合征中。在这项前瞻性、开放性临床试验中，我们评估了 16 例免疫缺陷患者和 16 例匹配的健康对照者（对照组）在接种三剂疫苗后的体液免疫反应和 T 细胞反应。本研究共纳入了 16 例免疫缺陷患者和 16 例匹配的健康对照者，这些对照者在第二次 COVID-19 疫苗接种后，抗 SARS-CoV-2 RBD（严重急性呼吸综合征冠状病毒 2 型受体结合域）抗体水平低于 1500 BAU/ml（结合抗体单位/毫升），定义为体液免疫反应欠佳，且符合接种第三剂 mRNA 疫苗的条件。接种后 4 周，对照组 100%和免疫缺陷/MBL 缺乏组 75%的患者抗 SARS-CoV-2 RBD 抗体水平>1500 BAU/ml，尽管差异无统计学意义（75%比 100%；p=0.109）。尽管与基线相比，接种后免疫缺陷/MBL 缺乏组患者的抗 SARS-CoV-2 RBD 抗体和中和抗体显著增加，但与对照组相比，这些反应在免疫缺陷/MBL 缺乏组患者中显著较低。值得注意的是，第三次接种增强了对野生型和 omicron 肽刺激的细胞免疫反应。在 4 周的随访期间，未报告严重不良事件，重要的是，疫苗接种对长期疾病活动度和疲劳几乎没有影响。这项试验强烈支持对免疫缺陷患者进行重复 COVID-19 疫苗接种的建议，尤其是当他们对疫苗最初的反应有限时。
