Distinct binding modes drive the broad neutralization profile of two persistent influenza hemagglutinin stem-specific antibody lineages.

• Tác giả: Sarah F Andrews, Gabriele Cerutti, Michael Chambers, Rebecca A Gillespie, Jason Gorman, Masaru Kanekiyo, Peter D Kwong, Grace E Mantus, Lawrence Shapiro, Chen-Hsiang Shen, Geoffrey D Shimberg, Abby Spangler, Tongqing Zhou
• Ngôn ngữ: eng
• Ký hiệu phân loại: 028 Reading and use of other information media
• Thông tin xuất bản: United States : Structure (London, England : 1993) , 2025
• Bộ sưu tập: NCBI
• ID: 726885
• Chủ đề: 1. Distinct; 2. Binding; 3. Modes

Tóm tắt

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.