Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
Lassa virus
antibody
challenge study
cryo-EM
nanoparticles
vaccine
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
14 12 2022
14 12 2022
Historique:
received:
08
04
2022
revised:
07
09
2022
accepted:
25
10
2022
pubmed:
19
11
2022
medline:
20
12
2022
entrez:
18
11
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36400021
pii: S1931-3128(22)00531-5
doi: 10.1016/j.chom.2022.10.018
pmc: PMC9794196
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Glycoproteins
0
Vaccines, Synthetic
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1759-1772.e12Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Y.W. has taken up a position at AstraZeneca; all experimental work was performed prior to this development.
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