Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens

oleh: George Ueda, Aleksandar Antanasijevic, Jorge A Fallas, William Sheffler, Jeffrey Copps, Daniel Ellis, Geoffrey B Hutchinson, Adam Moyer, Anila Yasmeen, Yaroslav Tsybovsky, Young-Jun Park, Matthew J Bick, Banumathi Sankaran, Rebecca A Gillespie, Philip JM Brouwer, Peter H Zwart, David Veesler, Masaru Kanekiyo, Barney S Graham, Rogier W Sanders, John P Moore, Per Johan Klasse, Andrew B Ward, Neil P King, David Baker

Format: Article
Diterbitkan: eLife Sciences Publications Ltd 2020-08-01

Deskripsi

Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. We first de novo designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.