Computational Design of Protein Nanoparticles Displaying Neuraminidase for Novel Influenza Vaccines

Abstract

Influenza virus is responsible for thousands of hospitalizations each year. Glycoproteins on the surface of the influenza virion, haemagglutinin (HA) and neuraminidase (NA), are crucial for viral entry and egress, respectively. Although neutralizing antibodies against HA inhibits infection, HA is a difficult target to effectively immunize against due to its propensity to accumulate escape mutations that evade the pre-existing immunity. NA is gaining attraction as a target for immunization due to its slower rate of mutation, as well as its ability to elicit broad, cross-reactive, and protective antibodies reducing influenza’s pathogenicity. Neutralizing antibody responses against NA are typically focused on the catalytic pocket site of NA; however, much of its antigenic landscape is unknown as researchers are still finding new immunologically relevant epitopes. Here, I set out to computationally design nanoparticles capable of displaying stabilized NA to make a vaccine capable of eliciting robust NA-specific neutralizing antibody titers. Successful deployment of this novel platform in mammalian cells may have a substantial impact in progressing candidate NA immunogens and present a promising avenue towards a universal influenza vaccine.