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接受B细胞清除疗法的抗中性粒细胞胞浆抗体相关性血管炎患者接种新型冠状病毒疫苗后的抗原特异性体液免疫和细胞免疫

Antigen Specific Humoral and Cellular Immunity Following SARS-CoV-2 Vaccination in ANCA-Associated Vasculitis Patients Receiving B-Cell Depleting Therapy.

作者信息

Marty Paige K, Van Keulen Virginia P, Erskine Courtney L, Shah Maleeha, Hummel Amber, Stachowitz Michael, Fatis Samantha, Granger Dane, Block Matthew S, Duarte-García Alí, Warrington Kenneth J, Theel Elitza S, Zhou Xian, Zeng Hu, Specks Ulrich, Escalante Patricio, Peikert Tobias

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, United States.

Department of Immunology, Mayo Clinic, Rochester, MN, United States.

出版信息

Front Immunol. 2022 Jan 28;13:834981. doi: 10.3389/fimmu.2022.834981. eCollection 2022.

Abstract

Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/μl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.

摘要

已知在接受B细胞靶向治疗的患者中,体液疫苗反应欠佳,而对于这些患者中疫苗诱导的T细胞免疫了解甚少。在本研究中,我们对接受抗CD20治疗的抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者在接种新冠疫苗后的体液和细胞抗原特异性抗SARS-CoV2反应进行了特征分析,这些患者在接种时要么B细胞耗竭,要么B细胞已恢复,同时还纳入了正常对照受试者。使用电化学发光免疫分析法检测SARS-CoV-2抗刺突(S)和抗核衣壳(NC)抗体,而使用干扰素-γ酶联免疫斑点(ELISPOT)分析法检测SARS-CoV-2对S糖蛋白亚基1(S1)和2(S2)以及受体结合域肽池的特异性T细胞反应。总共研究了26名近期接种疫苗的受试者。尽管缺乏可测量的体液免疫反应,但与B细胞已恢复的患者和正常对照相比,B细胞耗竭的患者产生了类似的疫苗诱导抗原特异性T细胞反应。我们的数据表明,为确保接受抗CD20治疗的患者产生体液反应,理想情况下应推迟接种SARS-CoV-2疫苗,直到B细胞恢复(CD-20阳性B细胞>10/μl)。然而,SARS-CoV-2疫苗接种在这些受试者中引发了强大的、可能具有保护作用的细胞免疫反应。需要进一步研究来确定疫苗诱导的抗SARS-CoV-2特异性T细胞免疫的持久性和保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7968/8831839/511f17546385/fimmu-13-834981-g001.jpg

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