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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Acceso en línea:https://doaj.org/article/3493c21b5fee4dc2a902a4cfd21185c1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:3493c21b5fee4dc2a902a4cfd21185c1
record_format dspace
spelling 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)
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
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
work_keys_str_mv AT kwintensliepen interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT edithschermer interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT iljabontjer interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT judithaburger interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT rekafelfodinelevai interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT philippmundsperger interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT philipjmbrouwer interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT monicatolazzi interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT atillafarsang interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT dietmarkatinger interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT johnpmoore interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT gabriellascarlatti interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT robinjshattock interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT quentinjsattentau interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
AT rogierwsanders interplayofdiverseadjuvantsandnanoparticlepresentationofnativelikehiv1envelopetrimers
_version_ 1718377377534312448