Cell host & microbe · 2022
Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
СтатьяНазвание и аннотация: Перевод в очереди
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Brouwer Philip J M, Antanasijevic Aleksandar, Ronk Adam J, Müller-Kräuter Helena, Watanabe Yasunori, Claireaux Mathieu, Perrett Hailee R, Bijl Tom P L, Grobben Marloes, Umotoy Jeffrey C, Schriek Angela I, Burger Judith A, Tejjani Khadija, Lloyd Nicole M, Steijaert Thijs H, van Haaren Marlies M, Sliepen Kwinten, de Taeye Steven W, van Gils Marit J, Crispin Max, Strecker Thomas, Bukreyev Alexander, Ward Andrew B, Sanders Rogier W
Аннотация
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.