The influenza virus remains a major health burden due to its abilities to change the epitopes of the major surface glycoprotein hemagglutinin, and its zoonotic nature, allowing transmission of animal viruses to humans to which the human population has no preexisting immunity. Although conserved hemagglutinin epitopes have been identified, there is a fundamental gap in understanding and correlating the disposition of influenza hemagglutinin epitopes on subunit vaccines and designed nanoparticles with immunogenicity. Lack of such information represents important problems and until they are addressed optimal display of conserved epitopes cannot be understood in molecular details. In FY 2016, we have continued designing and characterizing various nanoparticles displaying conserved epitopes from influenza hemagglutinins. In addition, we have established significant milestones in using computational methods with cryo-electron microscopy to determine the molecular organization and conformational state of hemagglutinin within influenza subunit vaccines. These results are significant and relevant to public health because it is expected to expand understanding of the structure and epitope disposition of influenza epitopes on traditional subunit vaccines and contemporary nanoparticles. This will aid immunogen evaluation and design for more efficacious season vaccines and facilitate the development of universal influenza vaccines.
