Post-exposure repertoires
Define the B-cell repertoire following infection and vaccination to clarify differences between the responses to natural infection compared with vaccination, which are relevant to inform broadly protective vaccination strategies.
Progress Highlights
León 2025 used negative stain electron microscopy polyclonal epitope mapping to structurally characterize IgG Ab responses to HA in individuals vaccinated with QIV or infected with IAVs during the 2018-2019 flu season and assess the prevalence of central stem-targeting Abs. Results identified IgGs targeting highly conserved regions (including stem and anchor) on H1 and H3 HAs and established a baseline for assessing polyclonal Ab responses in vaccination and infection.
Reis 2024 assessed the phenotypic and functional profile of H1N1 HA-specific B-cell response among participants who presented distinct immune response patterns prior to and after vaccination with the split-inactivated quadrivalent seasonal influenza virus vaccine (Fluzone, Sanofi).
Jia 2024 used serum from a RCT of seasonal TIV in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic and monitored for infection with pH1N1. Results suggested that seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive Abs with Fc potential without vaccination.
Boudreau 2023 applied a systems approach to profile HA- and NA-specific humoral signatures that track with the evolution of broad immunity in a cohort of vaccinated individuals and validate these findings in a second longitudinal cohort. Multivariate analysis revealed the presence of a unique pre-existing Fc-gamma-receptor-binding Ab profile in individuals that evolved broadly reactive HAI and suggesting that preexisting Fc-gamma-R2B binding Abs are a key correlate of the evolution of broadly protective influenza-specific Abs.
Einav 2023 developed a form of antigenic cartography (a neutralization landscape) that visualizes and quantifies Ab-virus interactions for Abs targeting the influenza HA stem, as a tool to analyze how an individual’s Ab repertoire evolves after vaccination or infection.