Mantus Grace E, Cerutti Gabriele, Chambers Michael, Gillespie Rebecca A, Shimberg Geoffrey D, Spangler Abby, Gorman Jason, Zhou Tongqing, Shen Chen-Hsiang, Kanekiyo Masaru, Kwong Peter D, Shapiro Lawrence, Andrews Sarah F
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
Structure. 2025 May 1;33(5):869-877.e7. doi: 10.1016/j.str.2025.02.010. Epub 2025 Mar 19.
Elicitation of antibodies to the influenza hemagglutinin stem is a critical part of universal influenza vaccine strategies. While numerous broadly reactive stem antibodies have been isolated, our understanding of how these antibodies mature within the human B cell repertoire is limited. Here, we isolated and tracked two stem-specific antibody lineages over a decade in a single participant that received multiple seasonal and pandemic influenza vaccinations. Despite similar binding and neutralization profiles, antibodies from these lineages utilized fundamentally different interactions to engage the central epitope on the influenza stem. Structural analysis of an unmutated common ancestor from one lineage identified critical residues that were the main drivers of increased affinity and breadth to group 1 influenza subtypes. These observations demonstrate the heterogeneous pathways by which stem-specific antibodies can mature within the human B cell repertoire.
诱导针对流感血凝素茎区的抗体是通用流感疫苗策略的关键部分。虽然已分离出许多具有广泛反应性的茎区抗体，但我们对这些抗体在人类B细胞库中如何成熟的了解有限。在此，我们在一名接受多次季节性和大流行性流感疫苗接种的参与者中，对两个茎区特异性抗体谱系进行了长达十年的分离和追踪。尽管这些谱系的抗体具有相似的结合和中和特征，但它们与流感病毒茎区中央表位的相互作用方式却截然不同。对其中一个谱系未发生突变的共同祖先进行结构分析，确定了关键残基，这些残基是增加对1组流感病毒亚型亲和力和广度的主要驱动因素。这些观察结果证明了茎区特异性抗体在人类B细胞库中成熟的异质性途径。
