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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection
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 ex...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794196/ https://www.ncbi.nlm.nih.gov/pubmed/36400021 http://dx.doi.org/10.1016/j.chom.2022.10.018 |
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author | 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. |
author_facet | 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. |
author_sort | Brouwer, Philip J.M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9794196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97941962023-01-09 Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection 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. Cell Host Microbe Article 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. Cell Press 2022-12-14 /pmc/articles/PMC9794196/ /pubmed/36400021 http://dx.doi.org/10.1016/j.chom.2022.10.018 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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. Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title_full | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title_fullStr | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title_full_unstemmed | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title_short | Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
title_sort | lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794196/ https://www.ncbi.nlm.nih.gov/pubmed/36400021 http://dx.doi.org/10.1016/j.chom.2022.10.018 |
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