Influenza viruses remains a major health burden due to their abilities to change the epitopes of their major surface glycoprotein hemagglutinin. 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 2019, we characterized the glycoprotein and virion organizations of influenza B viruses and the disposition of viral glycoprotein antigens within commercial influenza subunit vaccines with antigens for typed A and B influenza viruses. Also, we have continued both designing and characterizing various nanoparticles displaying conserved epitopes from influenza antigens, such as hemagglutinin as well as structurally mapping and identifying a novel pan H1 HA epitope within the head region. 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 A viruses. 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 nanoplatforms and HA. This will aid immunogen evaluation and design for more efficacious season vaccines and facilitate the development of universal influenza vaccines.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
City
State
Country
Zip Code
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
Gallagher, John R; Torian, Udana; McCraw, Dustin M et al. (2017) Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform. Virology 502:176-187
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
Dowd, Kimberly A; Ko, Sung-Youl; Morabito, Kaitlyn M et al. (2016) Rapid development of a DNA vaccine for Zika virus. Science 354:237-240
Yassine, Hadi M; Boyington, Jeffrey C; McTamney, Patrick M et al. (2015) Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med :
Harris, Audray K; Bartesaghi, Alberto; Milne, Jacqueline L S et al. (2013) HIV-1 envelope glycoprotein trimers display open quaternary conformation when bound to the gp41 membrane-proximal external-region-directed broadly neutralizing antibody Z13e1. J Virol 87:7191-6
Harris, Audray K; Meyerson, Joel R; Matsuoka, Yumiko et al. (2013) Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies. Proc Natl Acad Sci U S A 110:4592-7