Determining cross-neutralization properties of sera from individuals vaccinated with A/American wigeon/South Carolina/22-000345-001/2021 (SC21) strain-derived inactivated vaccine using lentivirus-based pseudoneutralization assays.

Highly pathogenic avian influenza (HPAI) H5N1 is a zoonotic virus that mainly circulates in waterfowl and poses serious risks to mammals, including humans, due to its ability to cause disease with a high fatality rate. Because humans lack H5-specific immunity, H5N1 remains a major pandemic concern. In 2024, H5N1 infections were detected in U.S. cattle, with growing reports of transmission to dairy farm workers. In November 2024, the first human case was confirmed in Canada. Individuals that work closely with birds or animals (e.g. farmers, park rangers and veterinarians) are at the highest risk of H5N1 infection. To prepare for the potential spread of H5N1, we need reliable tools to assess seroprevalence and pre-existing immunity to H5N1 arising from exposure to or vaccination against other influenza subtypes. The current standard tests for H5N1 antibodies require high-level containment facilities (CL3), making them slow and difficult to scale. A safer alternative uses harmless "pseudoviruses" that carry the H5N1 surface proteins HA and NA but lack the ability to replicate and infect. My research aims to develop a safe pseudovirus system to test how well sera samples from people vaccinated with the H5N1 strain SC21 can block infection by SC21 and by two newer H5N1 strains currently circulating in North America (TX24 and BC24). I will also use an Enzyme-Linked Lectin Assay to independently measure antibodies that target NA, which drives viral spread. Finally, I will assess how well seasonal H1N1 antibodies cross-react with H5N1. This work will enable a flexible system for rapidly evaluating immune protection against current and emerging H5N1 variants.