HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Sci Immunol. 2019 Apr 19;4(34). doi: 10.1126/sciimmunol.aau2710.
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.
诱导能够识别高度多样化株的抗体反应是开发 HIV 和流感等病毒疫苗的主要障碍。在这里，我们报告了用表达流感 H5 血凝素的复制型腺病毒 4 型重组病毒接种后，在单细胞水平上 B 细胞扩增和进化的动态。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，在可检测到的血清水平之外，H5 特异性抗体体细胞超突变和效力在活跃的病毒复制期过后几个月内持续增加。可以分离出个别广谱且有效的抗体，包括一种茎特异性抗体，它是一种新的多供体类别的一部分。这些结果表明，接种疫苗后，B 细胞反应会持续数月进行进化，在评估或增强疫苗诱导的免疫方面应加以考虑。
