肝移植受者第三次和第四次 SARS-CoV-2 mRNA 疫苗接种后的体液和细胞免疫反应。
Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients.
机构信息
Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
出版信息
Clin Gastroenterol Hepatol. 2022 Nov;20(11):2558-2566.e5. doi: 10.1016/j.cgh.2022.06.028. Epub 2022 Jul 16.
BACKGROUND & AIMS: Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations.
METHODS
In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders.
RESULTS
After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders.
CONCLUSIONS
A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.
背景与目的
与健康对照者（HCs）相比，肝移植受者（LTRs）在接受 2 剂严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）疫苗接种后，其免疫反应下降。在此，我们研究了额外疫苗接种的免疫原性。
方法
在这项前瞻性研究中，在第 3 次 mRNA 基于 SARS-CoV-2 疫苗接种后，106 例 LTRs 和第 4 次疫苗接种后 36 例 LTRs 中确定了体液（抗 SARS-CoV-2 受体结合域[抗-S RBD]）和细胞（干扰素-γ释放试验）免疫反应。将接种疫苗后抗-S RBD 抗体水平 >0.8 个任意单位（AU）/mL 的患者定义为应答者。
结果
第 3 次接种后，92%（97/106）的 LTRs 与 100%（28/28）的 HCs 相比为应答者。然而，与 HCs 相比，LTRs 的抗体滴度较低（1891.0 与 21857.0 AU/mL；P <.001）。在第 2 次和第 3 次接种之间（n=75），LTRs 的抗体水平中位数增加了 67 倍。在 2 次接种后血清阴性的患者中，第 3 剂诱导血清转化的比例为 76%（19/25），而所有 HCs 在第 2 次接种后均已呈血清阳性。与第 2 次接种相比，第 3 次接种后检测到 72%（28/39）的刺突特异性 T 细胞反应，而第 2 次接种后为 32%（11/34）。低抗体反应（抗-S RBD <100 AU/mL）的独立危险因素为肝移植后第 1 年内首次接种（优势比[OR]，8.00；P=.023）、估计肾小球滤过率 <45 mL/min（OR，4.72；P=.006）和淋巴细胞计数低（OR，5.02；P=.008）。第 4 次接种将中位数抗体水平提高了 9 倍，并使之前的非应答者中的 60%（3/5）发生血清转化。
结论
第 3 次和第 4 次 SARS-CoV-2 疫苗接种可有效提高 LTRs 的体液和细胞免疫反应，但程度低于 HCs。一般应考虑在 LTRs 中接种第 4 剂疫苗。
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