Thalhauser, Stefanie and Peterhoff, David and Wagner, Ralf and Breunig, Miriam (2020) Presentation of HIV-1 Envelope Trimers on the Surface of Silica Nanoparticles. JOURNAL OF PHARMACEUTICAL SCIENCES, 109 (1). pp. 911-921. ISSN 0022-3549, 1520-6017
Full text not available from this repository. (Request a copy)Abstract
Inducing immune responses protecting from HIV infection or at least controlling replication poses a huge challenge to modern vaccinology. An increasingly discussed strategy to elicit a potent and broad neutralizing antibody response is the immobilization of HIV's trimeric envelope (Env) surface receptor on a nanoparticulate carrier. As a conceptual proof, we attached an Env variant (BG505 SOSIP.664) to highly stable and biocompatible silica nanoparticles (SiNPs) via site-specific covalent conjugation or nonspecific adsorption to SiNPs. First, we demonstrated the feasibility of SiNPs as platform for Env presentation by a thorough characterization process during which Env density, attachment stability, and antigenicity were evaluated for both formulations. Binding affinities to selected antibodies were in the low nanomolar range for both formulations confirming that the structural integrity of Env is retained after attachment. Second, we explored the recognition of SiNP conjugates by antigen presenting cells. Here, the uptake of Env attached to SiNPs via a site-specific covalent conjugation was 4.5-fold enhanced, whereas adsorbed Env resulted only in a moderate 1.4-fold increase compared with Env in its soluble form. Thus, we propose SiNPs with site-specifically and covalently conjugated Env preferably in a high density as a promising candidate for further investigations as vaccine platform. (C) 2020 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADSORPTION; PARTICLES; ANTIGENS; CULTURE; CELLS; HIV/AIDS; vaccine delivery; silica; protein delivery; nanoparticle(s); envelope |
| 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 Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2021 08:37 |
| Last Modified: | 08 Apr 2021 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45534 |
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