EMD-25108
I53-50 nanoparticle core reconstructed from GPC-I53-50NP by focused refinement
EMD-25108
Single-particle3.67 Å
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Map released: 12/10/2022
Last modified: 16/10/2024
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
Sample: I53-50 nanoparticle core recovered from GPC-I53-50 nanoparticle
Fitted models: 7sge (Avg. Q-score: 0.479)
Deposition Authors: Antanasijevic A
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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
Brouwer PJM
,
Antanasijevic A
,
Ronk AJ
,
Muller-Krauter H
,
Watanabe Y,
Claireaux M,
Perrett HR
,
Bijl TPL,
Grobben M
,
Umotoy JC,
Schriek AI,
Burger JA,
Tejjani K,
Lloyd NM,
Steijaert TH,
van Haaren MM,
Sliepen K,
de Taeye SW,
van Gils MJ,
Crispin M
,
Strecker T
,
Bukreyev A,
Ward AB
,
Sanders RW
(2022) Cell Host Microbe , 30 , 1759
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(2022) Cell Host Microbe , 30 , 1759
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.
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.