IMMUNOLOGY2025™ Conference Recordings-Harnessing the ghosts of influenza past to generate protective humoral immunity

Harnessing the ghosts of influenza past to generate protective humoral immunity - Jenna Guthmiller

Video Transcription

Video Summary

Dr. Jenna Guthmiller discussed how influenza’s rapid evolution, antigenic drift/shift, and our own immune history make current seasonal vaccines only modestly effective. She explained that “imprinting” or preexisting memory B cells can both hinder and help, often steering responses toward variable, non-protective viral regions, but sometimes enabling broadly neutralizing antibodies. Her lab studies how prior exposure shapes recall responses to conserved hemagglutinin sites, especially the stalk, receptor-binding site, and anchor epitopes. She highlighted promising vaccine strategies, including chimeric HA vaccines, which boosted stalk-focused antibodies and memory B cells in humans. She also described work identifying rare cross-reactive memory B cells against emerging H5N1, including very broad naturally occurring antibodies. Finally, she noted nasal mucosa as an important site for local humoral immunity and suggested future vaccines may need to overcome immunodominance and target mucosal protection.

Keywords

influenza vaccine

antigenic drift

immune imprinting

hemagglutinin stalk

chimeric HA vaccine

mucosal immunity