Highly pathogenic H5N1 avian influenza viruses continue to cause sporadic human infections and remain a pandemic concern. New research (in press) suggests that this may be partly explained by variation in pre-existing cross-reactive antibodies.
In this study, researchers mapped H5N1 cross-reactive antibody responses in contemporary human populations and examined how prior influenza vaccination shapes this immunity. Using samples from two clinical cohorts, the team assessed whether pandemic H1N1 and seasonal influenza vaccines could enhance antibody responses that recognize H5N1.
They found that many individuals already carry low levels of antibodies capable of neutralizing H5N1, even without prior exposure. These antibodies correlated strongly with responses targeting conserved regions of influenza hemagglutinin, particularly the stalk domain, and were detected using a pseudovirus system that closely mirrored neutralization of authentic H5N1 viruses.
Importantly, vaccination with an AS03-adjuvanted pandemic H1N1 vaccine significantly increased H5N1 cross-reactive and neutralizing antibodies, especially in individuals with limited prior exposure to pandemic H1N1. In contrast, standard seasonal influenza vaccination had a more modest effect.
The study also showed that immune imprinting, shaped by an individual’s influenza exposure history, influenced the pattern of cross-reactive antibodies present before vaccination. This highlights how early immune experiences can shape responses to emerging viral threats.
Together, these findings suggest that certain influenza vaccines, particularly adjuvanted pandemic formulations, may enhance baseline population immunity against H5N1. This has important implications for pandemic preparedness and for understanding why some individuals may be better protected against severe avian influenza infection than others.
Journal article: Bonifaz, M.A., et al. 2026. Adjuvanted influenza vaccination increases pre-existing H5N1 cross-reactive antibodies. Nature Communications.
Summary by Stefan Botha
