Detectable plasma severe acute respiratory syndrome coronavirus 2 spike antigen is associated with poor antibody response following third messenger RNA vaccination in kidney transplant recipients.
Detectable plasma severe acute respiratory syndrome coronavirus 2 spike antigen is associated with poor antibody response following third messenger RNA vaccination in kidney transplant recipients.
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在肾移植受者中，可检测到的血浆严重急性呼吸综合征冠状病毒 2 刺突抗原与第三信使 RNA 疫苗接种后抗体反应不佳有关。
DOI：
10.1111/tid.14281
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Werbel,WilliamA
中科院分区：
文献类型：
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作者：
Karaba,AndrewH;Swank,Zoe;Hussain,Sarah;Chahoud,Margaret;Durand,ChristineM;Segev,DorryL;Robien,MarkA;Heeger,PeterS;Larsen,ChristianP;Tobian,AaronAR;Walt,DavidR;Werbel,WilliamA
背景肾移植受者（KTR）对基于信使RNA（mRNA）的严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）疫苗接种产生较低的抗体反应，但这种不良反应的精确机制仍不确定。一个潜在的贡献者是次优刺突抗原（sAg）的翻译和表达，由于移植免疫抑制，这可能会导致暴露不足，发展体液和/或细胞免疫responses.MethodsWithin单臂临床试验，65 KTR进行超灵敏血浆sAg测试之前，3和14天后，第三次mRNA疫苗剂量。在接种后14天和30天连续测量抗SARS CoV-2刺突抗体（抗受体结合结构域[抗RBD]）。sAg检测和临床因素之间的关联进行了评估。使用Wilcoxon秩和检验比较了有与无sAg表达的患者第30天的抗RBD滴度。ResultsOverall，16例（25%）KTR在接种疫苗后为sAg阳性（sAg+），在第3天达到峰值。sAg（+）与sAg（-）KTR的临床和实验室因素大致相似。sAg（+）状态与第30天抗RBD应答显著负相关，如果sAg（+），中位数（四分位数范围）为10.8（<0.4-338.3）U/mL，如果sAg（-），中位数为709（10.5-2309.5）U/mL（即，低66倍;结论血浆sAg不足不太可能导致KTR中抗体应答差，而sAg检测意味着免疫应答不足以从血液中快速清除疫苗抗原。应探索其他下游机制，如sAg运输和呈递。
BackgroundKidney transplant recipients (KTRs) generate lower antibody responses to messenger RNA (mRNA)‐based severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination, yet precise mechanisms for this poor response remain uncertain. One potential contributor is suboptimal spike antigen (sAg) translation and expression owing to transplant immunosuppression, which might lead to insufficient exposure to develop humoral and/or cellular immune responses.MethodsWithin a single‐arm clinical trial, 65 KTRs underwent ultrasensitive plasma sAg testing before, and 3 and 14 days after, the third mRNA vaccine doses. Anti‐SARS‐CoV‐2 spike antibodies (anti‐receptor binding domain [anti‐RBD]) were serially measured at 14 and 30 days post‐vaccination. Associations between sAg detection and clinical factors were assessed. Day 30 anti‐RBD titer was compared among those with versus without sAg expression using Wilcoxon rank sum testing.ResultsOverall, 16 (25%) KTRs were sAg positive (sAg+) after vaccination, peaking at day 3. Clinical and laboratory factors were broadly similar in sAg(+) versus sAg(‐) KTRs. sAg(+) status was significantly negatively associated with day 30 anti‐RBD response, with median (interquartile range) 10.8 (<0.4–338.3) U/mL if sAg(+) versus 709 (10.5–2309.5) U/mL if sAg(‐) (i.e., 66‐fold lower;p= .01).ConclusionInadequate plasma sAg does not likely drive poor antibody responses in KTRs, rather sAg detection implies insufficient immune response to rapidly clear vaccine antigen from blood. Other downstream mechanisms such as sAg trafficking and presentation should be explored.