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| Title | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection. |
|---|---|
| Journal, issue, pages | Cell Host Microbe, Vol. 30, Issue 12, Page 1759-1772.e12, Year 2022 |
| Publish date | Dec 14, 2022 |
 Authors | 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 Crispin / Thomas Strecker / Alexander Bukreyev / Andrew B Ward / Rogier W Sanders /     |
| PubMed 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 ...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. |
 External links | Cell Host Microbe / PubMed:36400021 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.67 - 4.41 Å |
| Structure data | EMDB-25107, PDB-7sgd: EMDB-25108, PDB-7sge: EMDB-25109, PDB-7sgf: |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords |  VIRAL PROTEIN / glycoprotein / Lassa / Josiah / vaccine design / nanoparticle / protein design / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |
lassa mammarenavirus
