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Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antige...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873233/ https://www.ncbi.nlm.nih.gov/pubmed/33563983 http://dx.doi.org/10.1038/s41541-021-00285-9 |
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author | Brouwer, Philip J. M. Antanasijevic, Aleksandar de Gast, Marlon Allen, Joel D. Bijl, Tom P. L. Yasmeen, Anila Ravichandran, Rashmi Burger, Judith A. Ozorowski, Gabriel Torres, Jonathan L. LaBranche, Celia Montefiori, David C. Ringe, Rajesh P. van Gils, Marit J. Moore, John P. Klasse, Per Johan Crispin, Max King, Neil P. Ward, Andrew B. Sanders, Rogier W. |
author_facet | Brouwer, Philip J. M. Antanasijevic, Aleksandar de Gast, Marlon Allen, Joel D. Bijl, Tom P. L. Yasmeen, Anila Ravichandran, Rashmi Burger, Judith A. Ozorowski, Gabriel Torres, Jonathan L. LaBranche, Celia Montefiori, David C. Ringe, Rajesh P. van Gils, Marit J. Moore, John P. Klasse, Per Johan Crispin, Max King, Neil P. Ward, Andrew B. Sanders, Rogier W. |
author_sort | Brouwer, Philip J. M. |
collection | PubMed |
description | The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. |
format | Online Article Text |
id | pubmed-7873233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78732332021-02-16 Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles Brouwer, Philip J. M. Antanasijevic, Aleksandar de Gast, Marlon Allen, Joel D. Bijl, Tom P. L. Yasmeen, Anila Ravichandran, Rashmi Burger, Judith A. Ozorowski, Gabriel Torres, Jonathan L. LaBranche, Celia Montefiori, David C. Ringe, Rajesh P. van Gils, Marit J. Moore, John P. Klasse, Per Johan Crispin, Max King, Neil P. Ward, Andrew B. Sanders, Rogier W. NPJ Vaccines Article The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Nature Publishing Group UK 2021-02-09 /pmc/articles/PMC7873233/ /pubmed/33563983 http://dx.doi.org/10.1038/s41541-021-00285-9 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Brouwer, Philip J. M. Antanasijevic, Aleksandar de Gast, Marlon Allen, Joel D. Bijl, Tom P. L. Yasmeen, Anila Ravichandran, Rashmi Burger, Judith A. Ozorowski, Gabriel Torres, Jonathan L. LaBranche, Celia Montefiori, David C. Ringe, Rajesh P. van Gils, Marit J. Moore, John P. Klasse, Per Johan Crispin, Max King, Neil P. Ward, Andrew B. Sanders, Rogier W. Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title_full | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title_fullStr | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title_full_unstemmed | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title_short | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles |
title_sort | immunofocusing and enhancing autologous tier-2 hiv-1 neutralization by displaying env trimers on two-component protein nanoparticles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873233/ https://www.ncbi.nlm.nih.gov/pubmed/33563983 http://dx.doi.org/10.1038/s41541-021-00285-9 |
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