EMD-25108

Single-particle
3.67 Å
EMD-25108 Deposition: 05/10/2021
Map released: 12/10/2022
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-25108

I53-50 nanoparticle core reconstructed from GPC-I53-50NP by focused refinement

EMD-25108

Single-particle
3.67 Å
EMD-25108 Deposition: 05/10/2021
Map released: 12/10/2022
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: synthetic construct
Sample: I53-50 nanoparticle core recovered from GPC-I53-50 nanoparticle
Fitted models: 7sge (Avg. Q-score: 0.479)

Deposition Authors: Antanasijevic A , Brouwer PJM
Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
PUBMED: 36400021
DOI: doi:10.1016/j.chom.2022.10.018
ISSN: 1934-6069
Abstract:
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.