Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
J Virol. 2018 Aug 16;92(17). doi: 10.1128/JVI.01024-18. Print 2018 Sep 1.
Since 2013, influenza A H7N9 virus has emerged as the most common avian influenza virus subtype causing human infection, and it is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of 45 H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5 to 4 months, 6 to 8 months, and 12 to 15 months postinfection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to the intensive care unit (ICU) and patients presenting with acute respiratory distress syndrome (ARDS) than in patients with mild disease. Frequencies of virus-specific gamma interferon (IFN-γ)-secreting T cells were lower in critically ill patients requiring ventilation than in patients without ventilation within 4 months after infection. The percentages of H7N9-specific IFN-γ-secreting T cells tended to increase over time in patients ≥60 years or in critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8 T cells expressing the lung-homing marker CD49a were observed at 6 to 8 months after H7N9 infection compared to those in samples obtained at 1.5 to 4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients and have implications for T cell-directed immunization strategies. Avian influenza A H7N9 virus remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus-specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8 T cells expressing the lung-homing marker CD49a were detected at 6 to 8 months after infection. Our results indicated a long-term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, which is relevant to the development of T cell-based universal influenza vaccines.
自 2013 年以来，甲型 H7N9 流感病毒已成为导致人类感染的最常见禽流感病毒亚型，其致死风险较高。然而，对于从 H7N9 感染中康复的患者的免疫记忆特征，我们还了解甚少。我们收集了一组 45 名 H7N9 幸存者的队列，对他们在感染后长达 15 个月的情况进行了随访。在感染后 1.5 至 4 个月、6 至 8 个月和 12 至 15 个月时，分析了他们的序贯样本中的体液和细胞免疫应答。H7N9 特异性抗体浓度随时间下降，在入住重症监护病房（ICU）的重病患者和出现急性呼吸窘迫综合征（ARDS）的患者中，保护性抗体的持续时间长于轻症患者。在感染后 4 个月内，需要通气的重症患者中病毒特异性γ干扰素（IFN-γ）分泌 T 细胞的频率低于未通气的患者。在≥60 岁的患者或需要通气的重症患者中，H7N9 特异性 IFN-γ分泌 T 细胞的百分比随时间推移而趋于增加。与感染后 1.5 至 4 个月时的样本相比，在感染后 6 至 8 个月时，观察到 H7N9 感染后表达归巢标志物 CD49a 的抗原特异性 CD8 T 细胞的百分比增加。我们的研究结果表明，在年龄较大或重症患者中，病毒特异性 T 细胞免疫的重建和演变时间延长，这对 T 细胞导向的免疫策略具有重要意义。甲型 H7N9 流感病毒仍然是对公共卫生的重大威胁。然而，以前没有研究确定从 H7N9 感染中康复的患者的病毒特异性 T 细胞免疫记忆的特征和动态。我们的研究结果表明，在年龄较大和病情较重的患者中，H7N9 感染后建立 H7N9 特异性 T 细胞记忆的时间延长。在感染后的前 4 个月，重症患者的 T 细胞反应较低，而随着时间的推移，年龄较大和重症患者的 T 细胞反应趋于增加。在感染后 6 至 8 个月时，检测到表达归巢标志物 CD49a 的抗原特异性 CD8 T 细胞的水平升高。我们的结果表明，H7N9 感染对病毒特异性记忆 T 细胞具有长期影响。这些发现加深了我们对 H7N9 感染后病毒特异性记忆 T 细胞免疫的动态变化的认识，这与开发基于 T 细胞的通用流感疫苗有关。
