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 nano-platforms with immunogenicity for the development of broader protecting seasonal vaccines and a universal influenza vaccine. 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 2015, we have continued designing and characterizing various nano-platforms displaying conserved epitopes from influenza hemagglutinins. We have established significant milestones both in using computational methods to design nanoparticles and to image by cryo-electron microscopy nanoparticles both without and bound with broadly neutralizing antibodies. 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 various nano-platforms that will aid immunogen design for universal influenza vaccines.
