Antibody responses in humans after infection with avian influenza viruses

摘要 人类经常接触季节性流感病毒，如H1N1、H3N2和B型流感病毒。 然而，感染H5N1或H7N9等禽流感病毒的情况很少见。到目前为止，还不清楚 人类免疫系统对这些病毒的暴露做出反应，特别是在先前存在的免疫环境中 季节性流感病毒株。初步数据显示，在这些罕见的情况下，针对表位的抗体 人类季节性流感病毒和禽流感病毒之间的保守性增强。在此协作环境中 徐实验室(上海复旦大学，中国)和克拉默实验室(伊坎)之间的合作 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。抗体反应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自然反应性和功能性。 感染了H7N9病毒。然后，在流行病学层面上，我们将评估“处于危险中”的交叉反应。 队列(菜市场小贩、禽鸟饲养员、农民等)为了深入了解暴露于 禽流感病毒。最后，我们将放大以表征单抗的表位用途 在感染禽流感病毒后诱导。本研究获得的数据将指导设计 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.