利妥昔单抗与疫苗的间隔对儿童 SARS-CoV-2 免疫原性的影响:先前自然感染的潜在作用。
Rituximab-to-vaccine interval on SARS-CoV-2 immunogenicity in children: The potential role of prior natural infection.
发表日期:2024 May
作者:
Renato Gualtieri, Sabine Yerly, Stephanie Garcia-Tarodo, Paloma Parvex, Nathalie Rock, Klara Posfay-Barbe, Arnaud M Didierlaurent, Christiane Eberhardt, Geraldine Blanchard-Rohner
来源:
Cellular & Molecular Immunology
摘要:
抗 CD20 抗体(利妥昔单抗)用于成人和儿童治疗各种自身免疫性疾病和肿瘤疾病。利妥昔单抗会消耗 B CD20 细胞,从而消除对疫苗的抗体反应。本研究旨在检查接受利妥昔单抗治疗的 5-18 岁儿童与健康匹配儿童相比,对基于 mRNA 的 COVID-19 疫苗的抗体反应。 2022 年 1 月 31 日至 7 月 18 日期间,我们在日内瓦大学进行了一项前瞻性观察研究医院招募接受利妥昔单抗治疗的 5-18 岁儿童,这些儿童已接受两剂基于 mRNA 的 SARS-CoV-2 疫苗。对照组是没有明显健康状况的健康志愿者。排除标准包括最近感染过 SARS-CoV-2。第二次疫苗接种后第 60 天 (±30) 和第 270 天 (±90) 采集血样。利妥昔单抗治疗组表现出 SARS-CoV 抗受体结合域 (RBD) 特异性抗体水平显着降低在第二次疫苗接种后 60 (±30) 天,比健康对照组的峰值 (S) 蛋白 -2(几何平均浓度:患者中为 868.3 IU/mL,对照中为 11,393 IU/mL;p = .008)。然而,利妥昔单抗与疫苗间隔短于 6 个月且有既往感染证据(基于阳性抗 N 抗体水平)的患者,其抗 RBD 抗体水平较高。既往感染 SARS-CoV- 2 可能会诱导抗 RBD 特异性记忆 B 细胞,即使在利妥昔单抗诱导的 B 细胞耗竭后,这些 B 细胞也可以通过 SARS-CoV-2 疫苗接种重新激活。这表明,有可能在利妥昔单抗注射后 6 个月内接种疫苗,以产生良好的抗体反应,特别是在过去感染过 SARS-CoV-2 的情况下。© 2024 作者。儿科过敏和免疫学由欧洲过敏和临床免疫学学会和约翰·威利出版
Treatment with anti-CD20 antibodies (rituximab) is used in both adults and children to treat various autoimmune and oncological diseases. Rituximab depletes B CD20+ cells and, thereby, antibody response to vaccines. This study aimed to examine the antibody response to mRNA-based COVID-19 vaccines in children aged 5-18 years undergoing rituximab treatment compared to healthy matched children.Between 31 January and 18 July 2022, we conducted a prospective observational study at the Geneva University Hospitals, enrolling children aged 5-18 years under rituximab treatment who had received two mRNA-based SARS-CoV-2 vaccine doses. Controls were healthy volunteers with no significant medical conditions. Exclusion criteria included a recent SARS-CoV-2 infection. Blood samples were collected at day 60 (±30) and day 270 (±90) after the second vaccination.The rituximab-treated group exhibited significantly lower levels of antibodies specific to the anti-receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein than healthy controls at 60 (±30) days after the second vaccine dose (geometric mean concentration: 868.3 IU/mL in patients and 11,393 IU/mL in controls; p = .008). However, patients with a rituximab-to-vaccine interval shorter than 6 months and with evidence of a past infection (based on positive anti-N antibody levels) had a high level of anti-RBD antibodies.A past infection with SARS-CoV-2 may induce anti-RBD-specific memory B cells that can be re-activated by SARS-CoV-2 vaccination, even after rituximab-induced B-cell depletion. This suggests that it is possible to vaccinate earlier than 6 months after rituximab to develop a good antibody response, especially in the case of past SARS-CoV-2 infection.© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.