Prolonged evolution of the memory B cell response induced by a replicating adenovirus-influenza H5 vaccine
Prolonged evolution of the memory B cell response induced by a replicating adenovirus-influenza H5 vaccine
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DOI：
10.1126/sciimmunol.aau2710
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发表时间：
2019-04-01
影响因子：
24.8
通讯作者：
Connors, Mark
中科院分区：
文献类型：
--
作者：
Matsuda, Kenta;Huang, Jinghe;Connors, Mark
诱导能够识别高度多样化毒株的抗体应答是开发诸如HIV和流感病毒的疫苗的主要障碍。在这里，我们报告的动态B细胞的扩增和进化在单细胞水平接种后的复制能力腺病毒4型重组病毒表达流感H5血凝素。荧光H1或H5探针用于定量和分离外周血B细胞及其抗原受体。我们观察到H5特异性抗体体细胞超突变和效力的增加超过了在血清水平上检测不到的活跃病毒复制期数月。可以分离出单个广泛而有效的抗体，包括一种干细胞特异性抗体，它是新的多供体类别的一部分。这些结果表明，B细胞应答在接种疫苗后数月内延长，在评估或增强疫苗诱导的免疫力时应予以考虑。
Induction of an antibody response capable of recognizing highly diverse strains is a major obstacle to the development of vaccines for viruses such as HIV and influenza. Here, we report the dynamics of B cell expansion and evolution at the single-cell level after vaccination with a replication-competent adenovirus type 4 recombinant virus expressing influenza H5 hemagglutinin. Fluorescent H1 or H5 probes were used to quantitate and isolate peripheral blood B cells and their antigen receptors. We observed increases in H5-specific antibody somatic hypermutation and potency for several months beyond the period of active viral replication that was not detectable at the serum level. Individual broad and potent antibodies could be isolated, including one stem-specific antibody that is part of a new multidonor class. These results demonstrate prolonged evolution of the B cell response for months after vaccination and should be considered in efforts to evaluate or boost vaccine-induced immunity.