Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27⁺⁺CD38⁺ plasmablasts. Whereas overall proportions of spike-reactive CD4⁺ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67⁺ and in vivo activated PD1⁺ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.

中文翻译：

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临时服用霉酚酸酯可增强肾移植受者的 SARS-CoV-2 疫苗接种特异性体液和细胞免疫

移植受者在接种 SARS-CoV-2 疫苗后表现出保护性免疫受损，这可能是由霉酚酸酯 (MPA) 免疫抑制引起的。来自自身免疫患者的最新数据表明，暂时保留 MPA 可能会显着改善加强疫苗接种的结果。我们在临时（5 周）MPA 保留期间向 29 名肾移植受者应用了第四剂 SARS-CoV-2 疫苗，这些受者对之前的疫苗接种没有产生体液免疫反应。在 76% 的患者中观察到疫苗接种后第 32 天的血清转化，这与获得病毒中和能力有关。有趣的是，21/25 (84%) 接受 CNI 治疗的患者有反应，但只有 1/4 接受贝拉西普治疗的患者。根据幽默的反应，⁺⁺ CD38 ⁺浆母细胞。尽管在第四次给药后尖峰反应性 CD4 ⁺ T 细胞的总体比例保持不变，但频率与特定 IgG 水平呈正相关。重要的是，在 MPA 保持期间再次接种疫苗后，抗原特异性增殖的 Ki67 ⁺和体内活化的 PD1 ⁺ T 细胞显着增加，而细胞因子的产生和记忆分化仍然不受影响。总之，MPA 保持是安全的，并且在加强疫苗接种期间增强了所有免疫力，这表明它在临床稳定移植受者的疫苗接种方案中实施。