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在 CoronaVac 三剂免疫方案中,风湿性疾病患者滤泡辅助 T 细胞的动态变化及随后的抗体反应。

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

机构信息

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

Immunology. 2023 Jan;168(1):184-197. doi: 10.1111/imm.13572. Epub 2022 Sep 19.

DOI:10.1111/imm.13572
PMID:36057099
Abstract

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

摘要

鉴于科兴疫苗(CoronaVac)的认可度不断提高,我们需要评估科兴疫苗在风湿性疾病(RD)患者中的安全性和免疫原性变化。在此,我们全面分析了接受三剂科兴疫苗免疫接种方案后的 RD 患者的体液和细胞反应。将病情稳定和/或疾病活动度低(n=40)的 RD 患者或健康对照者(n=40)按照 1:1 的比例随机分配接受科兴疫苗(科兴)。第二次和第三次接种后,健康对照者(HC)和 RD 患者的抗受体结合域(RBD)抗体和中和抗体的流行率相似。然而,与 HC 相比,RD 患者的抗-RBD IgG 和中和抗体滴度显著较低(p<0.05),这与滤泡辅助性 T 细胞(Tfh)反应受损有关。在 RD 患者中,与第一次和第二次接种后未产生抗体反应的患者相比,产生抗体反应的患者显示出更高的 Tfh 细胞(p<0.05)。有趣的是,血清学阴性反应者对 SARS-CoV-2 衍生肽的 Tfh 记忆反应与抗-RBD IgG 阳性者相似,而所有(4/4)HC 中的无反应者和 62.5%(5/8)RD 患者中的无反应者在第三次接种后均出现血清学阳性反应。未观察到严重不良事件。总之,我们的研究结果支持对病情稳定和/或疾病活动度低的 RD 患者进行 SARS-CoV-2 疫苗接种。RD 患者产生疫苗特异性抗体的能力受损与 Tfh 细胞诱导减少有关。在未来的研究中仍需要探索接种时间窗口。临床试验注册:本试验在中国临床试验注册中心注册,注册号 ChiCTR2100049138。

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