Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection

Philip J.M. Brouwer, Aleksandar Antanasijevic, Adam J. Ronk, Helena Müller-Kräuter, Yasunori Watanabe, Mathieu Claireaux, Hailee R. Perrett, Tom P.L. Bijl, Marloes Grobben, Jeffrey C. Umotoy, Angela I. Schriek, Judith A. Burger, Khadija Tejjani, Nicole M. Lloyd, Thijs H. Steijaert, Marlies M. van Haaren, Kwinten Sliepen, Steven W. de Taeye, Marit J. van Gils, Max CrispinThomas Strecker, Alexander Bukreyev, Andrew B. Ward, Rogier W. Sanders

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)1759-1772.e12
    JournalCell Host and Microbe
    Volume30
    Issue number12
    DOIs
    StatePublished - Dec 14 2022

    Keywords

    • Lassa virus
    • antibody
    • challenge study
    • cryo-EM
    • nanoparticles
    • vaccine

    ASJC Scopus subject areas

    • Parasitology
    • Microbiology
    • Virology

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