人感染H7N9禽流感病毒抗体持久性和细胞免疫应答的前瞻性队列研究

Human infection with H7N9 avian influenza virus has shown a high prevalence in winter and spring with a mortality of 40%, suggested that the H7N9 virus still pose a serious threat to human health. Because the population are generally naive to the H7N9 virus and the virus still pose a human pandemic potential, it is really important to determine the immune response to H7N9 infection as early as possible. In this project, a prospective cohort study will be employed to study the characteristics of immune response in human infected with H7N9 virus. We will enroll the H7N9 patients from areas where H7N9 infections had high prevalence, seasonal influenza patients, and general healthy population, and will prospectively follow the subjects during the 4-year period. We will examine the number of NK, DC, and T cells during early phase of the infection, antibodies level and the number of memory T and B cells at different intervals of infection, and will compare to the infection of seasonal influenza virus. In this project, our aims are: 1) to investigate the dynamics and persistence of antibodies, 2) to clarify kinetics of virus-specific CD8+ T cells and its relationship with viral shedding, 3) to characterize the immune memory signature after the virus infection, and 4) to analyze the relationship between immune response and disease severity. Our study would advance the optimization of serum epidemiological investigation of H7N9 virus, development of vaccine, and the prevention and control of the disease.

人感染H7N9禽流感病毒已呈现出冬春季节高发的流行特点，其病死率高，严重威胁人类健康。由于人群普遍对H7N9禽流感病毒缺乏免疫力，且病毒具有大流行的潜在威胁。因此，及早开展H7N9禽流感病毒感染免疫应答的研究具有非常重要的意义。本项目拟采用前瞻性队列研究设计，在我国人感染H7N9禽流感高发地区系统纳入H7N9患者为病例组，以季节性流感患者和一般健康人群为对照组，开展为期4年的随访研究。通过检测患者感染早期NK、DC、T细胞亚群数量、感染后不同时期血清中的抗体水平以及记忆性T和B细胞数量，并与季节性流感进行比较。掌握人感染H7N9禽流感抗体动力学及持久性；明确病毒特异性CD8+T细胞动力学以及其与病毒载量和消除的关系；阐述人感染H7N9禽流感患者记忆细胞免疫应答特征；分析机体免疫应答与疾病严重程度的关系。此研究结果将为H7N9病毒血清流行病学调查的优化、疫苗的研制以及疾病的防控提供科学依据。

人感染H7N9禽流感病毒已呈现出冬春季节高发的流行特点，其病死率高，严重威胁人类健康。由于人群普遍对H7N9禽流感病毒缺乏免疫力，且病毒具有大流行的潜在威胁。因此，开展H7N9禽流感病毒感染免疫应答的研究具有非常重要的意义。本项目采用队列研究设计，对H7N9患者病毒特异性体液和细胞免疫应答、禽和猪暴露人群H7N9病毒感染进行前瞻性随访研究。通过对H7N9患者的随访，发现大多数患者在感染早期产生了较强的抗体应答，在感染后1年约90%患者中和抗体滴度≥1:40，且血凝抗体>1:80时能够明显抑制病毒在小鼠体内复制；感染后3年仍有84.2%康复者中和抗体≥1:40，且绝大部分康复者仍存在病毒特异性记忆CD4和CD8 T细胞应答。通过对禽和猪暴露人群的随访，发现禽暴露人群感染H7N9的血清流行率远高于一般健康人群，且与活禽市场家禽中H7N9病毒流行率呈正相关；猪暴露人群未发现H7N9病毒感染的血清学证据。基于上述研究工作积累并在本项目的支持下我们还开展了新冠患者疫苗接种者前瞻性随访研究，发现大部分新冠患者记忆性免疫应答可维持1年，但康复者和疫苗接种者血清抗体对B.1.1.7和B.1.351变异株中和活性显著下降。上述研究结果为H7N9病毒和新型冠状病毒疫苗的研制及疾病的防控提供重要的科学依据。在本项目的支持下，项目负责人以第一或通讯作者在New England Journal of Medicine、Trends In Microbiology、Nature Communications、Clinical Infectious Diseases、Emerging Infectious Diseases、Journal of Infectious Diseases等国际著名学术期刊发表本项目标注SCI论文13篇，累计影响因子184，单篇最高91。

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