Background & Aims

Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking.

Methods

We longitudinally compared the humoral, as well as CD4+ and CD8+ T-cell, responses between LTRs (n = 24) and healthy controls (n = 19) after three (LTRs: n = 9 to 16; healthy controls: n = 9 to 14 per experiment) to four (LTRs: n = 4; healthy controls: n = 4) vaccine doses, including in-depth phenotypical and functional characterization.

Results

Compared to healthy controls, development of high antibody titers required a third vaccine dose in most LTRs, while spike-specific CD8+ T cells with robust recall capacity plateaued after the second vaccine dose, albeit with a reduced frequency and epitope repertoire compared to healthy controls. This overall attenuated vaccine response was linked to a reduced frequency of spike-reactive follicular T helper cells in LTRs.

Conclusion

Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTRs. Decisions regarding additional booster doses may thus be based on individual vaccine responses as well as evolution of novel variants of concern.

Impact and implications

Due to immunosuppressive medication, liver transplant recipients (LTR) display reduced antibody titers upon COVID-19 mRNA vaccination, but the impact on long-term immune memory is not clear. Herein, we demonstrate that after three vaccine doses, the majority of LTRs not only exhibit substantial antibody titers, but also a robust memory T-cell response. Additional booster vaccine doses may be of special benefit for a small subset of LTRs with inferior vaccine response and may provide superior protection against evolving novel viral variants. These findings will help physicians to guide LTRs regarding the benefit of booster vaccinations.

中文翻译：

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通过在肝移植受者中接种 mRNA 疫苗来增强受损的 SARS-CoV-2 特异性免疫力

背景与目标

肝移植受者 (LTR) 对 COVID-19 mRNA 疫苗接种的反应减弱；然而，缺乏对体液免疫和细胞免疫之间相互作用的详细了解，尤其是在第三次（和第四次）疫苗接种后。

方法

我们纵向比较了 LTR (n = 24) 和健康对照 (n = 19) 三个后的体液反应以及 CD4+ 和 CD8+ T 细胞反应（LTR：n = 9 至 16；健康对照：n = 9 至每个实验 14 个）到四个（LTR：n = 4；健康对照：n = 4）疫苗剂量，包括深入的表型和功能表征。

结果

与健康对照相比，大多数 LTR 中高抗体滴度的发展需要第三剂疫苗，而具有强大回忆能力的刺突特异性 CD8+ T 细胞在第二剂疫苗后趋于稳定，尽管与健康对照相比频率和表位库有所减少。这种整体减弱的疫苗反应与 LTR 中尖峰反应性滤泡 T 辅助细胞频率降低有关。

结论

在大多数 LTR 中，三剂 COVID-19 mRNA 疫苗会引起整体强烈的体液和细胞记忆反应。因此，关于额外加强剂量的决定可能基于个体疫苗反应以及关注的新变体的演变。

影响和启示

由于免疫抑制药物，肝移植受者 (LTR) 在接种 COVID-19 mRNA 后抗体滴度降低，但对长期免疫记忆的影响尚不清楚。在此，我们证明在接种三剂疫苗后，大多数 LTR 不仅表现出显着的抗体滴度，而且表现出强大的记忆 T 细胞反应。额外的加强疫苗剂量可能对一小部分疫苗反应较差的 LTR 有特殊好处，并可能提供针对不断发展的新型病毒变体的更好保护。这些发现将帮助医生指导 LTR 了解加强疫苗接种的好处。