Zhao Jingxian, Alshukairi Abeer N, Baharoon Salim A, Ahmed Waleed A, Bokhari Ahmad A, Nehdi Atef M, Layqah Laila A, Alghamdi Mohammed G, Al Gethamy Manal M, Dada Ashraf M, Khalid Imran, Boujelal Mohamad, Al Johani Sameera M, Vogel Leatrice, Subbarao Kanta, Mangalam Ashutosh, Wu Chaorong, Ten Eyck Patrick, Perlman Stanley, Zhao Jincun
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.
Sci Immunol. 2017 Aug 4;2(14). doi: 10.1126/sciimmunol.aan5393.
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4 and CD8 T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4 but not CD8 T cell responses; patients with higher PRNT and CD4 T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8 T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8 T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.
中东呼吸综合征冠状病毒(MERS-CoV)可引发高致死性肺炎。MERS最近被确定为疫苗研发的候选对象,但大多数研究工作都集中在抗体反应上,而在冠状病毒感染后,抗体反应往往是短暂的。冠状病毒特异性T细胞通常寿命较长,但MERS患者的病毒特异性T细胞反应尚未得到研究。我们从21名MERS幸存者身上获取了外周血单个核细胞和/或血清。我们在所有MERS幸存者中检测到了MERS-CoV特异性CD4和CD8 T细胞反应,并通过测量肽刺激后的细胞因子表达来证明其功能。体外测量的中和(PRNT)抗体滴度可预测感染小鼠血清的保护能力,且与CD4而非CD8 T细胞反应相关;PRNT和CD4 T细胞反应较高的患者在重症监护病房的停留时间更长,病毒脱落时间延长,且需要通气。MERS-CoV特异性抗体反应检测不到的幸存者产生的CD8 T细胞反应与整个队列相当。年龄、疾病严重程度、合并症与病毒特异性CD8 T细胞反应之间没有相关性。总之,测量MERS-CoV特异性T细胞反应可能有助于预测预后、监测疫苗疗效,以及在流行病学研究中识别轻症MERS患者,并将补充病毒特异性抗体测量。