Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

中文翻译：

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捉迷藏：流感病毒和 B 细胞之间的相互作用。

流感病毒在主要表面蛋白血凝素 (HA) 中不断获得基因突变/重配，导致产生具有抗原变异的菌株。然而，有一些 HA 表位在流感病毒中是保守的，并且被广泛的保护性抗体靶向。下一代流感疫苗的一个目标是刺激 B 细胞对这些保守表位的反应，以提供针对不同流感病毒的广泛保护。然而，具有广泛保护性的 B 细胞不容易被具有天然结构的 HA 抗原激活，因为病毒有多种策略可以逃避针对保守表位的体液免疫反应。一种这样的策略是通过空间位阻将保守的表位从 B 细胞监视中隐藏起来。人类 B 细胞抗原受体 (BCR) 谱分析的技术进步已将 BCR 分解为隐藏在天然结构中但被广泛保护性抗体靶向的 HA 表位。我们在此描述了广泛保护性抗体的特征和功能，以及使 B 细胞能够寻找这些隐藏表位的策略，对通用流感疫苗的开发具有潜在影响。