在接受疾病修正治疗的多发性硬化症患者中，国药（BBIBP-CorV）SARS-CoV-2 疫苗的免疫原性、临床疗效和安全性：一项前瞻性队列研究。
Immunogenicity, clinical efficacy, and safety of the sinopharm (BBIBP-CorV) SARS-CoV-2 vaccine among people with multiple sclerosis receiving disease-modifying therapies: a prospective cohort study.
机构信息
Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, 1419733141, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
BMC Neurol. 2024 Aug 20;24(1):291. doi: 10.1186/s12883-024-03793-y.
BACKGROUND
To investigate the safety (adverse events [AEs] and post-vaccination multiple sclerosis [MS] activity within 6 weeks), clinical efficacy (protection against coronavirus disease 2019 [COVID-19]), and vaccine-induced humoral immunogenicity (SARS-CoV-2 neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG) of the Sinopharm (BBIBP-CorV) vaccine among people with MS (PwMS) receiving different disease-modifying therapies (DMTs).
METHODS
This prospective cohort study was conducted between November 2021 and May 2022. PwMS were followed for six months after the 2nd dose of vaccination. Antibody responses were measured 2-16 weeks after the 2nd dose injection. Multivariate logistic regression was employed to assess the impact of each DMT on dichotomous antibody responses, adjusting for age, sex, MS phenotype, expanded disability status scale, disease duration, and vaccination-antibody titration interval.
RESULTS
Among the 261 screened PwMS, 209 (aged 38.23 ± 9.73 years, female: 70.8%; relapsing-remitting MS: 80.4%) were included. The frequencies of experiencing non-serious AEs and post-vaccination MS activity were 66.0% and 4.8%, respectively. Breakthrough COVID-19 infection was observed in 14.8% of the PwMS. A subcohort of 125 PwMS was assessed for antibody responses. Positive neutralizing antibodies, anti-nucleocapsid IgG, and anti-spike IgG were detected in 36.8%, 35.2%, and 52.0% of the PwMS, respectively. Multivariate regression indicated a 96% (OR: 0.04 [95% CI: 0.00, 0.51], P = 0.013), 93% (OR: 0.07 [0.01, 0.64], P = 0.019), and 89% (OR: 0.11 [0.01, 0.96], P = 0.045) reduced odds of positive neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG, respectively, among fingolimod-receivers. Additionally, anti-CD20s-receivers had 88% (OR: 0.12 [0.02, 0.85], P = 0.034) lower odds of being positive for anti-nucleocapsid IgG.
CONCLUSIONS
BBIBP-CorV appeared to be well tolerated in PwMS, with promising clinical efficacy. However, a suboptimal humoral response was observed in PwMS receiving fingolimod and anti-CD20s. Future research should investigate the relationship between humoral responses and the frequency and severity of COVID-19 infection across various DMTs.
背景
本研究旨在探究接种新型冠状病毒肺炎（Corona Virus Disease 2019，COVID-19）灭活疫苗（Sinopharm，BBIBP-CorV）后，多发性硬化症（Multiple Sclerosis，MS）患者的安全性（不良事件和接种后 6 周内的 MS 活动）、临床疗效（预防 COVID-19）和体液免疫原性（SARS-CoV-2 中和抗体、抗核衣壳 IgG 和抗刺突 IgG），并分析不同疾病修正治疗（Disease-Modifying Therapy，DMT）对体液免疫应答的影响。
方法
本前瞻性队列研究于 2021 年 11 月至 2022 年 5 月进行。在接种第 2 剂疫苗后，对 PwMS 进行 6 个月的随访。在第 2 剂接种后 2-16 周检测抗体反应。采用多变量逻辑回归分析评估每种 DMT 对二分类抗体应答的影响，调整因素包括年龄、性别、MS 表型、扩展残疾状况量表、疾病持续时间和疫苗-抗体滴定间隔。
结果
在 261 例筛查的 PwMS 中，209 例（年龄 38.23±9.73 岁，女性：70.8%；缓解-复发型 MS：80.4%）被纳入研究。非严重不良事件的发生率为 66.0%，接种后 MS 活动的发生率为 4.8%。14.8%的 PwMS 发生突破性 COVID-19 感染。对 125 例 PwMS 进行了抗体应答亚组评估。36.8%、35.2%和 52.0%的 PwMS 检测到了阳性中和抗体、抗核衣壳 IgG 和抗刺突 IgG。多变量回归分析显示，与接受芬戈莫德治疗的患者相比，接受 fingolimod 治疗的患者的中和抗体、抗核衣壳 IgG 和抗刺突 IgG 阳性的优势比（OR）分别为 0.04（95%置信区间：0.00，0.51），0.07（0.01，0.64）和 0.11（0.01，0.96），差异有统计学意义（P 值分别为 0.013、0.019 和 0.045）。此外，接受抗 CD20s 治疗的患者抗核衣壳 IgG 阳性的优势比为 0.88（95%置信区间：0.02，0.85），差异有统计学意义（P=0.034）。
结论
BBIBP-CorV 对 PwMS 似乎具有良好的耐受性，临床疗效良好。然而，接受 fingolimod 和抗 CD20s 治疗的 PwMS 观察到体液免疫应答不理想。未来的研究应进一步探究不同 DMT 下体液免疫应答与 COVID-19 感染频率和严重程度的关系。
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