Antibody responses in humans after infection with avian influenza viruses

摘要 人类经常暴露于季节性流感病毒，如H1N1、H3N2和流感B病毒。 然而，禽流感病毒如H5N1或H7N9的感染是罕见的。到目前为止，尚不清楚 人体免疫系统对暴露于这些病毒作出反应，特别是在预先存在的免疫力的情况下 季节性流感病毒株。初步数据表明，在这些罕见的情况下， 在人类季节性流感病毒和禽流感病毒之间保守的基因得到加强。在这次合作中 徐实验室（复旦大学，上海，中国）和Krammer实验室（伊坎 美国纽约西奈山医学院）我们建议研究人类抗体反应 在自然感染禽流感病毒后。抗体应答将在三个水平上进行表征。 首先，我们将评估人类多克隆血清反应的反应性和功能性， 感染H7N9病毒。然后，在流行病学水平上，我们将评估“处于危险中”的交叉反应性。 群体（湿货市场商贩、鸟类处理者、农民等）以深入了解暴露于 禽流感病毒。最后，我们将放大以表征单克隆抗体的表位使用 感染禽流感病毒后诱发。本研究获得的数据将指导 新的广泛保护性和大流行性流感病毒疫苗，将大大加强我们的大流行 做好准备

Abstract Humans are frequently exposed to seasonal influenza viruses like H1N1, H3N2 and influenza B viruses. However, infections with avian influenza viruses like H5N1 or H7N9 are rare. So far it is unclear how the human immune system reacts to exposure to these viruses, specifically in the context of pre-existing immunity to seasonal influenza virus strains. Preliminary data has shown that in these rare cases antibodies to epitopes that are conserved between human seasonal and avian influenza viruses are boosted. In this collaborative effort between the Xu laboratory (Fudan University, Shanghai, China) and the Krammer laboratory (Icahn School of Medicine at Mount Sinai, New York, USA) we propose to investigate the human antibody response after natural infection with avian influenza viruses. Antibody responses will be characterized at three levels. Initially we will assess the reactivity and functionality of polyclonal serum responses of humans naturally infected with H7N9 viruses. Then, on an epidemiologic level, we will assess the cross-reactivity of 'at risk' cohorts (wet market vendors, bird handlers, farmers etc.) to get insights into the prevalence of exposure to avian influenza viruses. Finally, we will zoom in to characterize the epitope usage of monoclonal antibodies induced after infection with avian influenza viruses. The data obtained from this study will guide the design of novel broadly protective and pandemic influenza virus vaccines and will significantly enhance our pandemic preparedness.