Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers
Abstract The immunogenicity of HIV-1 envelope (Env) trimers is generally poor. We used the clinically relevant ConM SOSIP trimer to compare the ability of different adjuvants (squalene emulsion, ISCOMATRIX, GLA-LSQ, and MPLA liposomes) to support neutralizing antibody (NAb) responses in rabbits. The...
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Nature Portfolio
2021
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oai:doaj.org-article:3493c21b5fee4dc2a902a4cfd21185c12021-12-02T18:51:50ZInterplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers10.1038/s41541-021-00364-x2059-0105https://doaj.org/article/3493c21b5fee4dc2a902a4cfd21185c12021-08-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00364-xhttps://doaj.org/toc/2059-0105Abstract The immunogenicity of HIV-1 envelope (Env) trimers is generally poor. We used the clinically relevant ConM SOSIP trimer to compare the ability of different adjuvants (squalene emulsion, ISCOMATRIX, GLA-LSQ, and MPLA liposomes) to support neutralizing antibody (NAb) responses in rabbits. The trimers were administered as free proteins or on nanoparticles. The rank order for the adjuvants was ISCOMATRIX > SE > GLA-LSQ ~ MPLA liposomes > no adjuvant. Stronger NAb responses were elicited when the ConM SOSIP trimers were presented on ferritin nanoparticles. We also found that the GLA-LSQ adjuvant induced an unexpectedly strong antibody response to the ferritin core of the nanoparticles. This “off-target” effect may have compromised its ability to induce the more desired antitrimer antibodies. In summary, both adjuvants and nanoparticle display can improve the magnitude of the antibody response to SOSIP trimers but the best combination of trimer presentation and adjuvant can only be identified experimentally.Kwinten SliepenEdith SchermerIlja BontjerJudith A. BurgerRéka Felfödiné LévaiPhilipp MundspergerPhilip J. M. BrouwerMonica TolazziAtilla FarsangDietmar KatingerJohn P. MooreGabriella ScarlattiRobin J. ShattockQuentin J. SattentauRogier W. SandersNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-8 (2021) |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kwinten Sliepen Edith Schermer Ilja Bontjer Judith A. Burger Réka Felfödiné Lévai Philipp Mundsperger Philip J. M. Brouwer Monica Tolazzi Atilla Farsang Dietmar Katinger John P. Moore Gabriella Scarlatti Robin J. Shattock Quentin J. Sattentau Rogier W. Sanders Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
description |
Abstract The immunogenicity of HIV-1 envelope (Env) trimers is generally poor. We used the clinically relevant ConM SOSIP trimer to compare the ability of different adjuvants (squalene emulsion, ISCOMATRIX, GLA-LSQ, and MPLA liposomes) to support neutralizing antibody (NAb) responses in rabbits. The trimers were administered as free proteins or on nanoparticles. The rank order for the adjuvants was ISCOMATRIX > SE > GLA-LSQ ~ MPLA liposomes > no adjuvant. Stronger NAb responses were elicited when the ConM SOSIP trimers were presented on ferritin nanoparticles. We also found that the GLA-LSQ adjuvant induced an unexpectedly strong antibody response to the ferritin core of the nanoparticles. This “off-target” effect may have compromised its ability to induce the more desired antitrimer antibodies. In summary, both adjuvants and nanoparticle display can improve the magnitude of the antibody response to SOSIP trimers but the best combination of trimer presentation and adjuvant can only be identified experimentally. |
format |
article |
author |
Kwinten Sliepen Edith Schermer Ilja Bontjer Judith A. Burger Réka Felfödiné Lévai Philipp Mundsperger Philip J. M. Brouwer Monica Tolazzi Atilla Farsang Dietmar Katinger John P. Moore Gabriella Scarlatti Robin J. Shattock Quentin J. Sattentau Rogier W. Sanders |
author_facet |
Kwinten Sliepen Edith Schermer Ilja Bontjer Judith A. Burger Réka Felfödiné Lévai Philipp Mundsperger Philip J. M. Brouwer Monica Tolazzi Atilla Farsang Dietmar Katinger John P. Moore Gabriella Scarlatti Robin J. Shattock Quentin J. Sattentau Rogier W. Sanders |
author_sort |
Kwinten Sliepen |
title |
Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
title_short |
Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
title_full |
Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
title_fullStr |
Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
title_full_unstemmed |
Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers |
title_sort |
interplay of diverse adjuvants and nanoparticle presentation of native-like hiv-1 envelope trimers |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/3493c21b5fee4dc2a902a4cfd21185c1 |
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