Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients,Clinical Gastroenterology and Hepatology

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Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients
Clinical Gastroenterology and Hepatology ( IF 11.6 ) Pub Date : 2022-07-16 , DOI: 10.1016/j.cgh.2022.06.028
Aenne Harberts ₁ , Golda M Schaub ₂ , Darius F Ruether ₁ , Paul M Duengelhoef ₃ , Thomas T Brehm ₂ , Hendrik Karsten ₁ , Anahita Fathi ₄ , Jacqueline Jahnke-Triankowski ₅ , Lutz Fischer ₅ , Marylyn M Addo ₄ , Friedrich Haag ₃ , Marc Luetgehetmann ₆ , Ansgar W Lohse ₂ , Julian Schulze Zur Wiesch ₂ , Martina Sterneck ₇

Affiliation

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.
Institute of Immunology, 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; Bernhard-Nocht-Institute for Tropical Medicine, Department for Clinical Immunology of Infectious Diseases, Hamburg, Germany; University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD), Hamburg, Germany.
Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

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.

中文翻译：

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

背景与目标

与健康对照组 (HCs) 相比，肝移植受者 (LTRs) 在接种 2 次严重急性呼吸综合征冠状病毒 2 型 (SARS-CoV-2) 疫苗后免疫反应降低。在这里，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 106 例 106第三次接种后的 LTR 和第四次接种后的 36 个 LTR。接种疫苗后抗 S RBD 抗体水平 >0.8 任意单位 (AU)/mL 的患者被定义为应答者。

结果

接种 3 次后，92% (97/106) 的 LTR 与 100% (28/28) 的 HC 为应答者。然而，与 HCs 相比，LTRs 的抗体滴度较低（1891.0 vs 21,857.0 AU/mL；P < .001）。在第二次和第三次疫苗接种之间（n = 75），LTR 中的中位抗体水平增加了 67 倍。在 2 次疫苗接种后呈血清反应阴性的患者中，第 3 剂可诱导 76% (19/25) 的血清转化，而所有 HC 在 2 次疫苗接种后已呈血清反应阳性。第三次接种后，72% (28/39) 检测到尖峰特异性 T 细胞反应，而第二次接种后为 32% (11/34)。低抗体反应（抗 S RBD <100 AU/mL）的独立危险因素是肝移植后第一年内首次接种疫苗（优势比 [OR]，8.00；P = .023)，估计肾小球滤过率 <45 mL/min (OR, 4.72; P = .006)，淋巴细胞计数低 (OR, 5.02; P = .008 )。第四次疫苗接种导致 60% (3/5) 的先前无反应者中位抗体水平和血清转化增加了 9 倍。