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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.

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.

SUBMITTER: Brouwer PJM

PROVIDER: S-EPMC9794196 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.

Brouwer Philip J M PJM Antanasijevic Aleksandar A Ronk Adam J AJ Müller-Kräuter Helena H Watanabe Yasunori Y Claireaux Mathieu M Perrett Hailee R HR Bijl Tom P L TPL Grobben Marloes M Umotoy Jeffrey C JC Schriek Angela I AI Burger Judith A JA Tejjani Khadija K Lloyd Nicole M NM Steijaert Thijs H TH van Haaren Marlies M MM Sliepen Kwinten K de Taeye Steven W SW van Gils Marit J MJ Crispin Max M Strecker Thomas T Bukreyev Alexander A Ward Andrew B AB Sanders Rogier W RW

Cell host & microbe 20221117 12

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 ...[more]

PMID: 36400021

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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.

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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.

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