新型冠狀病毒疫苗對於紅斑性狼瘡病人的 T細胞免疫反應

Abstract

研究目的 紅斑性狼瘡（Systemic lupus erythematosus）是系統性自體免疫疾病的典型代表。由於高端疫苗在台灣的安全性和有效性得到確認，許多患者因安全考量選擇接種該疫苗而非messenger RNA (mRNA)疫苗。目前風濕免疫疾病患者的疫苗推薦是根據對於早期流感和肺炎鏈球菌疫苗的抗體反應研究，然而細胞免疫反應則較少報告。本研究旨在探討紅斑性狼瘡病人在蛋白次單位疫苗和mRNA疫苗接種後的細胞免疫反應。 方法 自2022年3月起，共有18名紅斑性狼瘡患者接受mRNA疫苗接種，14名患者接受蛋白次單位疫苗接種，我們從其全血樣本中分離出周邊單核球（peripheral blood mononuclear cells）進行T-SPOT® Discovery™ SARS-CoV-2檢測。此方法藉由干擾素的分泌測定T細胞反應強度，並以各孔中形成的斑點（spot forming units, SFU）計算，超過10個SFUs的反應則判定為陽性。 結果 兩組疫苗組病人之間在基本特徵、疾病活性和目前使用的免疫抑制藥物方面均沒有明顯差異。兩組的T細胞免疫反應數值上並沒有達到統計顯著的差異。然而，邏輯式回歸分析顯示蛋白次單位疫苗組對棘蛋白產生T細胞陽性反應的勝算比較低。 結論 我們的研究結果顯示，多劑量接種疫苗策略能夠增強T細胞反應。在紅斑性狼瘡的病人中，蛋白次單位疫苗引起的T細胞免疫反應相比mRNA疫苗較低；且蛋白次單位疫苗、較高的血紅素和類固醇劑量可能是紅斑性狼瘡病人族群降低T細胞陽性反應的影響因素。

Objectives Systemic lupus erythematosus (SLE) is the prototype systemic autoimmune disease. Many patients in Taiwan received MVC-COV1901 instead of messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines due to its safety and effectiveness. Current vaccine recommendations in autoimmune inflammatory rheumatic diseases (AIIRD) patients are mainly based on humoral responses to influenza and pneumococcal vaccination in humans. However, T cell responses were less discussed. Our study aimed to investigate the cellular immune responses after protein subunit vaccines or mRNA vaccines. Methods 18 patients with SLE who received mRNA vaccines and 14 patients who received protein subunit vaccine were enrolled since March 2022. Peripheral blood mononuclear cells (PBMCs) were isolated from their whole blood sample for T-SPOT® Discovery™ SARS-CoV-2 assay. Interferon response was calculated as spot forming units (SFU) in each well. A positive T cell response was defined as exceeding 10 SFUs per 250,000 PBMCs. Results There were no differences in baseline characteristics, disease activity, and current immunosuppressive medicine between two vaccine groups. Additionally, no statistical difference in T cell response was observed between the two groups. However, logistic regression indicated a trend towards decreased positive T cell responses to the spike protein in the protein subunit group. Conclusion Our study indicates that the T cell response can be augmented by multi-dose vaccination strategy. The protein subunit vaccines yielded a comparatively lower level of T cell response to mRNA vaccines. The protein subunit vaccines, higher hemoglobin level and steroid doses were significantly associated with a reduced positive T cell response among SLE patients.