A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = _0.090.13_0.18). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = _1.001.45_2.13); however, importantly, this seemingly protective tendency disappeared (aOR = _0.470.73_1.12) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = _2.394.26_7.92 for mTORi+tacrolimus; _2.345.54_15.32 for mTORi-only; and _6.7810.25_15.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = _0.811.54_2.98 for MMF + mTORi; and _0.811.51_2.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

中文翻译：

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mTOR 抑制剂、霉酚酸酯和其他免疫抑制方案对实体器官移植受者 SARS-CoV-2 mRNA 疫苗抗体反应的影响


最近的一项研究得出结论，服用 mTOR 抑制剂 (mTORi) 的移植患者的 SARS-CoV-2 mRNA 疫苗反应得到改善。这可能对移植患者的疫苗策略产生深远的影响；然而，研究设计的局限性引起了人们对结论的担忧。为了更强有力地解决这个问题，在对混杂因素进行适当调整的大型队列中，我们进行了各种基于回归和机器学习的分析，以比较全国队列中免疫抑制剂的抗体反应（ n = 1037）。 MMF 与抗体阳性反应的几率显着降低相关 (aOR = _0.09 0.13 _0.18 )。与最近的 mTORi 研究一致，mTORi 的几率往往更高 (aOR = _1.00 1.45 _2.13 )；然而，重要的是，在调整 MMF 后，这种看似保护性的趋势消失了 (aOR = _0.47 0.73 _1.12 )。我们通过免疫抑制剂的组合重复了这种比较。与 MMF + 他克莫司相比，无 MMF 方案与较高的阳性抗体反应几率相关（mTORi+他克莫司的 aOR = _2.39 4.26 _7.92 ；仅 mTORi 的_{aOR = 2.34} 5.54 _15.32 ；仅他克莫司的 aOR _{= 6.78} 10.25 _15.93 ），而 MMF -无论是否使用 mTORi，包括方案都不是（MMF + mTORi 的 aOR = _0.81 1.54 _2.98 ；仅 MMF 的 aOR _{= 0.81} 1.51 _2.87 ）。我们在一个独立队列 ( n = 512) 中重复了这些分析，并发现了类似的结果。 我们的研究表明，最近报告的发现与 MMF 相混淆，并且 mTORi 与疫苗反应改善并不独立相关。