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Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery

The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm an...

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Autores principales: Peterhoff, David, Thalhauser, Stefanie, Sobczak, Jan M., Mohsen, Mona O., Voigt, Christoph, Seifert, Nicole, Neckermann, Patrick, Hauser, Alexandra, Ding, Song, Sattentau, Quentin, Bachmann, Martin F., Breunig, Miriam, Wagner, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230641/
https://www.ncbi.nlm.nih.gov/pubmed/34208059
http://dx.doi.org/10.3390/vaccines9060642
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author Peterhoff, David
Thalhauser, Stefanie
Sobczak, Jan M.
Mohsen, Mona O.
Voigt, Christoph
Seifert, Nicole
Neckermann, Patrick
Hauser, Alexandra
Ding, Song
Sattentau, Quentin
Bachmann, Martin F.
Breunig, Miriam
Wagner, Ralf
author_facet Peterhoff, David
Thalhauser, Stefanie
Sobczak, Jan M.
Mohsen, Mona O.
Voigt, Christoph
Seifert, Nicole
Neckermann, Patrick
Hauser, Alexandra
Ding, Song
Sattentau, Quentin
Bachmann, Martin F.
Breunig, Miriam
Wagner, Ralf
author_sort Peterhoff, David
collection PubMed
description The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant.
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spelling pubmed-82306412021-06-26 Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery Peterhoff, David Thalhauser, Stefanie Sobczak, Jan M. Mohsen, Mona O. Voigt, Christoph Seifert, Nicole Neckermann, Patrick Hauser, Alexandra Ding, Song Sattentau, Quentin Bachmann, Martin F. Breunig, Miriam Wagner, Ralf Vaccines (Basel) Article The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant. MDPI 2021-06-11 /pmc/articles/PMC8230641/ /pubmed/34208059 http://dx.doi.org/10.3390/vaccines9060642 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peterhoff, David
Thalhauser, Stefanie
Sobczak, Jan M.
Mohsen, Mona O.
Voigt, Christoph
Seifert, Nicole
Neckermann, Patrick
Hauser, Alexandra
Ding, Song
Sattentau, Quentin
Bachmann, Martin F.
Breunig, Miriam
Wagner, Ralf
Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title_full Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title_fullStr Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title_full_unstemmed Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title_short Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
title_sort augmenting the immune response against a stabilized hiv-1 clade c envelope trimer by silica nanoparticle delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230641/
https://www.ncbi.nlm.nih.gov/pubmed/34208059
http://dx.doi.org/10.3390/vaccines9060642
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