Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies
Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies
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DOI：
10.1038/s41467-019-11821-6
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发表时间：
2019-08-28
影响因子：
16.6
通讯作者：
Takahashi, Yoshimasa
中科院分区：
文献类型：
--
作者：
Adachi, Yu;Tonouchi, Keisuke;Takahashi, Yoshimasa
在病毒复制位点的生殖中心（GC）B细胞获得对免疫原性差但保守的流感血凝素（HA）表位的特异性。这里，局部GC B细胞的高通量表位作图用于鉴定保守的HA表位，选择介导异亚型保护的交叉反应性抗体。该表位的独特特征是在病毒复制期间在低pH条件下暴露于融合后HA结构中的天然三聚体HA结构中的闭塞。重要的是，通过融合后HA抗原的全身免疫导致靶向封闭表位的GC B细胞，并诱导一类具有跨组特异性并提供不依赖于病毒中和活性的保护的保护性抗体。此外，这类广泛保护性抗体在较晚的时间点产生并持续存在。我们的研究结果确定了一类在病毒复制位点选择的交叉保护性抗体，并提供了使用封闭表位的疫苗策略的见解。
Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.