Peterhoff, David and Thalhauser, Stefanie and Sobczak, Jan M. and Mohsen, Mona O. and Voigt, Christoph and Seifert, Nicole and Neckermann, Patrick and Hauser, Alexandra and Ding, Song and Sattentau, Quentin and Bachmann, Martin F. and 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 (6): 642. ISSN , 2076-393X
Full text not available from this repository. (Request a copy)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 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENHANCING HUMORAL RESPONSES; NEUTRALIZING ANTIBODIES; GERMINAL CENTER; VACCINE; CELLS; HIV vaccine; silica nanoparticles; stabilized envelope trimer; Env |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Aug 2022 12:37 |
| Last Modified: | 29 Aug 2022 12:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46460 |
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