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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

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 and Wagner, Ralf (2021) Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery. Vaccines 9 (642), pp. 1-24.

Date of publication of this fulltext: 12 Jan 2022 16:48
Article
DOI to cite this document: 10.5283/epub.44328


Abstract

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 ...

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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Details

Item typeArticle
Journal or Publication TitleVaccines
Publisher:MDPI
Place of Publication:BASEL
Volume:9
Number of Issue or Book Chapter:642
Page Range:pp. 1-24
Date11 June 2021
InstitutionsMedicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann)
Identification Number
ValueType
10.3390/vaccines9060642DOI
KeywordsENHANCING HUMORAL RESPONSES; NEUTRALIZING ANTIBODIES; GERMINAL CENTER; VACCINE; CELLS; HIV vaccine; silica nanoparticles; stabilized envelope trimer; Env
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
600 Technology > 615 Pharmacy
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-443285
Item ID44328

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