Tan Eunice X, Lim Wen Hui, Thong Elizabeth, Chavatte Jean-Marc, Zhang Jinyan, Lim Jonathan, Jin Jocelyn Y, Lim Daniel R X, Kang Jaclyn Y T, Tang Ansel Shao Pin, Chan Kai En, Tan Caitlyn, Tan Shi Ni, Nah Benjamin, Huang Daniel Q, Wang Lin-Fa, Tambyah Paul A, Somani Jyoti, Young Barnaby, Muthiah Mark D
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
Transplant Direct. 2023 Sep 20;9(10):e1537. doi: 10.1097/TXD.0000000000001537. eCollection 2023 Oct.
Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.
All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.
Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response ( = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections ( < 0.001).
Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.
免疫功能低下个体被排除在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）信使核糖核酸疫苗的里程碑式研究之外。在此类患者中，与免疫功能正常的患者相比，疫苗接种反应可能减弱且消退更快。我们研究了2021年4月28日至2022年4月28日期间接受至少2剂信使核糖核酸疫苗的冠状病毒病2019疫苗接种的肝移植（LT）患者中，与SARS-CoV-2疫苗接种抗体反应降低相关的因素以及后续突破性感染的危险因素。
所有LT受者均接受至少2剂间隔21天的BNT162b2（辉瑞BioNTech）疫苗。我们使用罗氏电化学发光免疫分析法检测针对SARS-CoV-2刺突蛋白受体结合域的SARS-CoV-2刺突蛋白的抗体反应，并在接种第一剂和第二剂疫苗之前以及第二剂疫苗接种后2至3个月之间通过替代病毒中和试验（cPass）检测中和抗体的存在情况。
93名接受2剂BNT162b2的LT受者纳入分析。距LT的平均时间为110±154个月。2剂疫苗接种后，38.7%（36/93）的LT受者在cPass检测中为疫苗无反应者，而罗氏S检测中为20.4%（19/93）。多变量分析显示，年龄增加和他克莫司谷浓度升高与中和抗体反应不佳相关（分别为P=0.038和0.022）。联合使用抗代谢物疗法和他克莫司接近统计学意义（比值比0.21；95%置信区间，0.180-3.72；P=0.062）。88名LT受者中有18名（20.4%）发生突破性感染。女性性别与突破性感染独立相关（P<0.001）。
在LT受者中，年龄较大和他克莫司谷浓度较高与2剂SARS-CoV-2疫苗接种的免疫反应较差相关。需要进一步研究以评估与突破性感染相关的变量，从而确定哪些人应优先接受加强疫苗接种。
