新的动物流感病毒出现,发起大流行,并成为地方性的季节性变异体,这些变异体已经进化为逃避普遍的群体免疫。这些过程通常超过疫苗引发的保护。将免疫应答集中在保守表位上可以赋予持久的免疫力。我们描述了一个专注的,保护性抗体反应,丰富的记忆和血清库,到流感病毒血凝素(HA)头部界面的保守区域。11个例子的结构,8在这里报道,来自七个人供体的人证明了在单个表位上的反应的收敛。这11个基因多样,一个班级有一个共同点,IGκV1-39,轻链。所有抗体结合来自多种血清型的HA。缺乏明显的遗传限制和多种血清型引起的潜力可能解释了它们的丰度。我们将头部界面定义为广泛保护性抗体的主要靶标,可能影响流感病毒感染的结果。重要性在流行的人类流感病毒中突变的快速出现和逃避群体免疫的选择需要预测可能的变异以每年更新流感疫苗。识别流感病毒血凝素(HA)上的保守表面的人抗体的鉴定促使人们努力设计可以选择性地引发此类抗体的免疫原。最近发现了对两个HA“头”(球状,刺样三聚体顶端的受体结合结构域)为这些努力增加了新的靶标。我们报告了八种这样的抗体的结构,绑定HA头,并将它们相互比较,并与之前描述的其他三个进行比较。虽然基因多样,它们都聚集在一个共同的结合位点上。这里的分析可以指导临床前试验的免疫原设计。
Novel animal influenza viruses emerge, initiate pandemics, and become endemic seasonal variants that have evolved to escape from prevalent herd immunity. These processes often outpace vaccine-elicited protection. Focusing immune responses on conserved epitopes may impart durable immunity. We describe a focused, protective antibody response, abundant in memory and serum repertoires, to a conserved region at the influenza virus hemagglutinin (HA) head interface. Structures of 11 examples, 8 reported here, from seven human donors demonstrate the convergence of responses on a single epitope. The 11 are genetically diverse, with one class having a common, IGκV1-39, light chain. All of the antibodies bind HAs from multiple serotypes. The lack of apparent genetic restriction and potential for elicitation by more than one serotype may explain their abundance. We define the head interface as a major target of broadly protective antibodies with the potential to influence the outcomes of influenza virus infection. IMPORTANCE The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction of likely variants for an annual updating of influenza vaccines. The identification of human antibodies that recognize conserved surfaces on the influenza virus hemagglutinin (HA) has prompted efforts to design immunogens that might selectively elicit such antibodies. The recent discovery of a widely prevalent antibody response to the conserved interface between two HA \"heads\" (the globular, receptor-binding domains at the apex of the spike-like trimer) has added a new target for these efforts. We report structures of eight such antibodies, bound with HA heads, and compare them with each other and with three others previously described. Although genetically diverse, they all converge on a common binding site. The analysis here can guide immunogen design for preclinical trials.