The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.

H7N9流感病毒在人类中引起高致死性疾病，但尚无有效的治疗方法。在这里，我们报告了一种人类单克隆抗体m826，该抗体与H7血凝素（HA）结合并保护免受H7N9感染。m826在酸性pH下以亚纳摩尔亲和力与H7N9 HA结合，在中性pH下以低10倍的亲和力结合。与H7N9 HA复合的m826的高分辨率（1.9Å）晶体结构表明m826结合了一个抗原决定簇，该抗原决定簇在pH诱导的HA构象变化中可能完全暴露。m826通过可能涉及抗体依赖性细胞介导的细胞毒性的机制，完全保护小鼠免受H7N9病毒的致命攻击。有趣的是，免疫遗传学分析表明m826是种系抗体，并且可以在感染H7N9的患者，健康成年人和新生婴儿中鉴定出m826样序列。