Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

Abstract 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. Multivale...

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Autores principales:	Philip J. M. Brouwer, Aleksandar Antanasijevic, Marlon de Gast, Joel D. Allen, Tom P. L. Bijl, Anila Yasmeen, Rashmi Ravichandran, Judith A. Burger, Gabriel Ozorowski, Jonathan L. Torres, Celia LaBranche, David C. Montefiori, Rajesh P. Ringe, Marit J. van Gils, John P. Moore, Per Johan Klasse, Max Crispin, Neil P. King, Andrew B. Ward, Rogier W. Sanders
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d
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spelling	oai:doaj.org-article:6d2ce266cff0455eb80fcc32049d700d2021-12-02T14:26:46ZImmunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles10.1038/s41541-021-00285-92059-0105https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00285-9https://doaj.org/toc/2059-0105Abstract 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.Philip J. M. BrouwerAleksandar AntanasijevicMarlon de GastJoel D. AllenTom P. L. BijlAnila YasmeenRashmi RavichandranJudith A. BurgerGabriel OzorowskiJonathan L. TorresCelia LaBrancheDavid C. MontefioriRajesh P. RingeMarit J. van GilsJohn P. MoorePer Johan KlasseMax CrispinNeil P. KingAndrew B. WardRogier W. SandersNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Philip J. M. Brouwer Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
description	Abstract 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	article
author	Philip J. M. Brouwer Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders
author_facet	Philip J. M. Brouwer Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders
author_sort	Philip J. M. Brouwer
title	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_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_sort	immunofocusing and enhancing autologous tier-2 hiv-1 neutralization by displaying env trimers on two-component protein nanoparticles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d
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Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

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