Torque teno 病毒 DNA 载量作为预测肺移植受者对三剂 COVID-19 mRNA 疫苗基于抗体反应的标志物。

Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients.

机构信息

Virology Laboratory, Strasbourg University Hospital, Strasbourg, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg, France.

Department of Pneumology, Strasbourg Lung Transplant Program, Strasbourg University Hospital, Strasbourg, France.

出版信息

J Heart Lung Transplant. 2022 Oct;41(10):1429-1439. doi: 10.1016/j.healun.2022.07.008. Epub 2022 Jul 16.

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 log 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 log 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.

背景

先前的研究报告称，肺移植受者（LTR）对两剂 COVID-19 疫苗的反应不佳，但缺乏关于第三剂的相关数据。我们调查了 LTR 接种三剂 mRNA 疫苗后的抗体反应及其预测因素。

方法

共随访了 136 例 LTR，包括 10 例既往感染的 LTR 和 126 例 COVID-19 初治 LTR，在接种三剂 mRNA 疫苗期间和之后进行了随访。我们回顾性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评估了疫苗反应与患者特征之间的关联，包括普遍存在的 Torque teno 病毒（TTV）的病毒 DNA 载量（VL）（由 ROC 曲线分析确定的最佳截断值），这反映了整体免疫抑制情况。

结果

接种 3 剂后，126 例 COVID-19 初治 LTR 中有 47 例（37.3%）抗 RBD IgG 阳性（有反应者），其中 14 例（11.1%）抗体滴度高于 264 结合抗体单位/mL。与 10 例既往感染的 LTR 中的 7 例相比，没有中和 omicron 变异体。非应答与接种前 TTV VL ≥6.2 log 拷贝/mL 相关（优势比（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）和 BNT162b2（n=34；vs mRNA-1273，n=101）疫苗（OR=6.72，CI95=1.75-25.92）。在第二剂无反应者中，接种第三剂前 TTV VL ≥6.2 或<3.2 log 拷贝/mL 与低（0/19）和高（9/10）血清转化率相关。