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-Structure paper
タイトル | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection. |
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ジャーナル・号・ページ | Cell Host Microbe, Vol. 30, Issue 12, Page 1759-1772.e12, Year 2022 |
掲載日 | 2022年12月14日 |
著者 | 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 要旨 | 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. |
リンク | Cell Host Microbe / PubMed:36400021 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.67 - 4.41 Å |
構造データ | EMDB-25107, PDB-7sgd: EMDB-25108, PDB-7sge: EMDB-25109, PDB-7sgf: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / glycoprotein (糖タンパク質) / Lassa / Josiah (ヨシヤ) / vaccine design (ワクチン) / nanoparticle (ナノ粒子) / protein design (タンパク質設計) / VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) |