BACKGROUND

Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors.

METHODS

A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression.

RESULTS

After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 log₁₀ copies/mL before vaccination (Odds Ratio (OR) = 17.87, 95% confidence interval (CI95) = 3.02-105.72), mycophenolate treatment (OR = 4.73, CI95 = 1.46-15.34) and BNT162b2 (n = 34; vs mRNA-1273, n = 101) vaccine (OR = 6.72, CI95 = 1.75-25.92). In second dose non-responders, TTV VL ≥6.2 or <3.2 log₁₀ copies/mL before the third dose was associated with low (0/19) and high (9/10) rates of seroconversion.

CONCLUSION

COVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.

中文翻译：

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Torque teno 病毒 DNA 载量作为肺移植受者对三剂 COVID-19 mRNA 疫苗方案抗体反应的预测标志物

背景

先前的研究报告称，肺移植受者 (LTR) 对两剂 COVID-19 疫苗反应不佳，但缺乏有关第三剂的数据。我们调查了 LTR 中三剂 mRNA 疫苗后的抗体反应及其预测因素。

方法

在接种三剂 mRNA 疫苗期间和之后，共有 136 名 LTR，包括 10 名先前感染的 LTR 和 126 名未感染 COVID-19 的 LTR。我们回顾性地测量了抗受体结合域 (RBD) IgG 反应和中和抗体。在事后分析中，我们使用多变量逻辑回归模型来评估疫苗反应与患者特征之间的关联，包括无处不在的 Torque teno 病毒 (TTV) 的病毒 DNA 载量 (VL)（通过 ROC 曲线分析设置的最佳截止值） , 这反映了整体免疫抑制。

结果

3 剂后，47/126 (37.3%) 的 COVID-19 初治 LTR 具有阳性抗 RBD IgG（应答者），14/126（11.1%）的抗体滴度高于 264 结合抗体单位/mL。与之前感染的 10 个 LTR 中的 7 个相比，没有人中和 omicron 变体。无反应与疫苗接种前TTV VL ≥6.2 log ₁₀拷贝/mL（比值比 (OR) = 17.87，95% 置信区间 (CI95) = 3.02-105.72），霉酚酸酯治疗（OR = 4.73，CI95 = 1.46-15.34）相关和 BNT162b2（n = 34；对比 mRNA-1273，n = 101）疫苗（OR = 6.72，CI95 = 1.75-25.92）。在第二剂无应答者中，第三剂前 TTV VL ≥6.2 或 <3.2 log ₁₀拷贝/mL 与低 (0/19) 和高 (9/10) 血清转化率相关。

结论

COVID-19 幼稚 LTR 对三剂 mRNA 疫苗反应不佳，尤其是那些具有高 TTV VL 的疫苗。未来的研究可以进一步评估这种生物标志物作为疫苗策略的指南。