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 influenza epitopes have been identified, there is a fundamental gap in understanding and correlating the disposition of conserved influenza 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 influenza epitopes cannot be understood in molecular details. In FY 2018, we have continued both designing and characterizing various nanoparticles displaying conserved epitopes from influenza antigens, such as hemagglutinin. In addition, we have established significant milestones in the design, purification, 3D structural analysis, and animal efficacy studies of nanoplatforms that have conserved epitopes from both group 1 and group 2 influenza viruses. Furthermore, we have structurally characterized symmetrical nanoparticles and non-symmetrical particles, such as influenza virus-like particles (VLPs), as platforms to carry and display influenza antigens. These results are significant and relevant to public health because they are expected to expand understanding of the structure and epitope disposition of influenza epitopes on nanoplatforms. This will aid immunogen evaluation and design for more efficacious seasonal vaccines and facilitate the development of universal influenza vaccines.

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6
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2018
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Gallagher, John R; McCraw, Dustin M; Torian, Udana et al. (2018) Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy. Vaccines (Basel) 6:
McCraw, Dustin M; Gallagher, John R; Torian, Udana et al. (2018) Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization. Sci Rep 8:10342
Gallagher, John R; Torian, Udana; McCraw, Dustin M et al. (2017) Structural studies of influenza virus RNPs by electron microscopy indicate molecular contortions within NP supra-structures. J Struct Biol 197:294-307
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McCraw, Dustin M; Gallagher, John R; Harris, Audray K (2016) Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms. Clin Vaccine Immunol 23:483-95
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