Engineering influenza HA nanoparticles to better understand their immune responses and improve vaccine design

Abstract

Protein nanoparticle-based vaccines are a promising platform, shown to be efficacious in preventing disease against a variety of pathogens. Building on their success, increasing our understanding of how nanoparticle vaccines elicit immune responses will aid both in our general understanding of immunology and also in designing improved vaccines. This work centers on influenza hemagglutinin (HA) nanoparticle vaccine design. It starts with the design of HA ‘trihead’ nanoparticle vaccines, that incorporate several layers of immune refocusing to increase breadth and potency in responses elicited against the HA head. Trihead design was then adapted onto several strains of HA, with the ultimate goal of creating a new platform for seasonal influenza vaccines. Lastly, the interaction of antibodies and HA ectodomain nanoparticles was explored as a means to elucidate mechanisms of their immunogenicity.