Immune memory shapes human polyclonal antibody responses to H2N2 vaccination

• DOI: 10.1101/2023.08.23.554525
• Publication Date: 2023-08-25T00:45:27Z
• Authors: Yuhe R. Yang; Julianna Han; Hailee R. Perrett; Sara T. Richey; Abigail M. Jackson; Alesandra J. Rodr...; Rebecca A. Gillespie; Sarah O’Connell; Julie E. Raab; Lauren Y. Cominsky; Ankita Chopde; Masaru Kanekiyo; Katherine V. Houser; Grace L. Chen; Adrian B. McDermott; Sarah F. Andrews; Andrew B. Ward
• Keywords: Polyclonal antibodies; Immunological memory

Summary Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. recent phase I clinical trial investigating ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural biochemical characterization of immune memory on breadth diversity polyclonal serum antibody response elicited after vaccination. We temporally map epitopes targeted by antibodies first second vaccinations show previous exposure results higher responses to variable head domain while initial participants are dominated targeting conserved epitopes. use cryo-EM monoclonal B cell isolation describe molecular details cross-reactive including receptor binding site new vulnerability deemed medial junction. Our findings accentuate impact pre-existing responses. Highlights Serum Abs H2-F vaccination donors bound HA stem RBS-targeting VH1-69 were induced individuals The junction is previously uncharacterized epitope