心脏移植受者接种 COVID-19 疫苗后的病毒特异性免疫反应特征

Marina M. Zafranskaya, D. B. Nizheharodava, O. G. Shatova, I. I. Russkih, A. V. Velichko, M. I. Vanslau, S. F. Novitskaya, T. L. Denisevich, M. G. Kolyadko, E. Kurlyanskaya
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摘要

由于潜在的免疫抑制和并发症,心脏移植患者发生 COVID-19 感染不良后果的风险增加。迄今为止,所有针对各种 COVID-19 疫苗的大规模随机对照试验都不包括实体器官移植受者。因此,使用 COVID-19 疫苗预防心脏移植患者冠状病毒感染的有效性和安全性尚未得到充分研究。本研究对心脏移植患者接种疫苗(Vero 细胞双联疫苗和 Sputnik Light 强化疫苗)后的病毒特异性免疫反应进行了评估。在没有 COVID-19 病史的接种过疫苗的心脏移植患者中,从接种第二剂疫苗后的 4-6 个月开始,观察到 S 蛋白水平的抗体增加,并在接种后 9-12 个月内保持显著的统计学差异(无论是否接种了加强疫苗)。然而,抗体浓度仍然很低,37% 的患者检测不到抗体。与血清阴性患者相比,在接种过 COVID-19 疫苗的心脏移植患者中,接种后的免疫力伴随着在接种后的动态过程中维持高水平的 SARS-CoV-2 病毒 S 蛋白的病毒特异性 IgG 抗体,在加强免疫后的 9-12 个月中,这些抗体的增加具有统计学意义。在整个随访期间,对 SARS-CoV-2 病毒 S 蛋白的特异性细胞反应(根据 CD3⁺154⁺和 CD3⁺IFNγ⁺TNFα⁺细胞的评估)仍然很低、在接种第二剂疫苗 4-6 个月后,有 COVID-19 病史的患者的尖峰反应淋巴细胞数量发生了显著变化。这与体液反应的评估结果一起表明,具有混合免疫力的患者接种疫苗后会产生更明显的免疫力。在为心脏移植患者制定疫苗接种策略的风险和收益评估方法时,应考虑临床疗效、罕见严重不良事件的持续监测以及疫苗免疫原性数据。
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Characteristics of virus-specific immunological reactions following COVID-19 vaccination in heart transplant recipients
Heart transplant patients are at an increased risk of COVID-19 infection adverse outcomes because of underlying immunosuppression and concomitant comorbidities. To date, all large-scale randomized controlled trials for various COVID-19 vaccines have excluded solid organ transplant recipients. Therefore, the efficacy and safety of coronavirus infection prevention using COVID-19 vaccines in transplant heart patients has not been sufficiently studied. In this research, the evaluation of virus-specific immunological reactions after vaccination (double Vero Cell vaccination and Sputnik Light booster vaccination) in heart transplant patients has been carried out. In vaccinated heart transplant individuals who did not have a history of COVID-19, starting from 4–6 months after the 2nd dose of the vaccine, an increase in antibodies to S protein level of was observed, while maintaining statistically significant differences for 9–12 months after vaccination (regardless of whether with or without booster vaccination). However, the concentration of antibodies remained low, and 37% of patients detected no antibodies. In vaccinated heart transplant individuals following the previous COVID-19 infection, as compared to seronegative patients, post-vaccination immunity is accompanied by maintaining a high level of virus-specific IgG antibodies to the S protein of the SARS-CoV-2 virus in the dynamics of the post-vaccination period with a statistically significant increase of these antibodies by 9–12 months after booster vaccination. The specific cellular response (according to the assessment of CD3⁺154⁺ and CD3⁺IFNγ⁺ TNFα⁺ cells) to the S protein of the SARS-CoV-2 virus remained low throughout the entire follow-up period, was recorded in 5–40% of heart transplant patients and statistically significant changes in the number of spikereactive lymphocytes were observed in patients with a history of COVID-19 by 4–6 months after administration of the 2nd dose of the vaccine. This, together with the results of the assessment of the humoral response, indicates a more pronounced post-vaccination immunity in patients with a hybrid immunity. While developing a methodology for assessing the risk and benefit of a vaccination strategy for individual heart transplant patients, clinical efficacy, ongoing monitoring of rare serious adverse events, and data on vaccine immunogenicity should be taken into account.
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