EMD-21169
De novo designed tetrahedral nanoparticle T33_dn2 presenting BG505-SOSIP
EMD-21169
Single-particle34.17 Å
Deposition: 05/01/2020Map released: 12/08/2020
Last modified: 19/08/2020
Sample Organism:
synthetic construct
Sample: Tetrahedral nanoparticle, T33_dn2, presenting BG505-SOSIP
Deposition Authors: Ward AB, Antanasijevic A
Sample: Tetrahedral nanoparticle, T33_dn2, presenting BG505-SOSIP
Deposition Authors: Ward AB, Antanasijevic A
Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens.
Ueda G 
,
Antanasijevic A ,
Fallas JA,
Sheffler W,
Copps J,
Ellis D,
Hutchinson GB ,
Moyer A,
Yasmeen A,
Tsybovsky Y,
Park YJ ,
Bick MJ ,
Sankaran B,
Gillespie RA,
Brouwer PJ ,
Zwart PH,
Veesler D ,
Kanekiyo M,
Graham BS ,
Sanders RW,
Moore JP,
Klasse PJ ,
Ward AB ,
King NP,
Baker D
(2020) eLife , 9
,
Antanasijevic A ,
Fallas JA,
Sheffler W,
Copps J,
Ellis D,
Hutchinson GB ,
Moyer A,
Yasmeen A,
Tsybovsky Y,
Park YJ ,
Bick MJ ,
Sankaran B,
Gillespie RA,
Brouwer PJ ,
Zwart PH,
Veesler D ,
Kanekiyo M,
Graham BS ,
Sanders RW,
Moore JP,
Klasse PJ ,
Ward AB ,
King NP,
Baker D
(2020) eLife , 9
Abstract:
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.
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.