Direkt zum Inhalt

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

Veröffentlichungsdatum dieses Volltextes: 12 Jan 2022 16:48
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.44328


Zusammenfassung

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.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftVaccines
Verlag:MDPI
Ort der Veröffentlichung:BASEL
Band:9
Nummer des Zeitschriftenheftes oder des Kapitels:642
Seitenbereich:S. 1-24
Datum11 Juni 2021
InstitutionenMedizin > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische Biologie (Prof. Heilmann)
Identifikationsnummer
WertTyp
10.3390/vaccines9060642DOI
Stichwörter / KeywordsENHANCING HUMORAL RESPONSES; NEUTRALIZING ANTIBODIES; GERMINAL CENTER; VACCINE; CELLS; HIV vaccine; silica nanoparticles; stabilized envelope trimer; Env
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-443285
Dokumenten-ID44328

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