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J Pharm Sci. 2019 Nov 1. pii: S0022-3549(19)30731-2. doi: 10.1016/j.xphs.2019.10.059. [Epub ahead of print]

Presentation of HIV-1 Env trimers on the surface of silica nanoparticles.

Author information

1
Department of Pharmaceutical Technology, University Regensburg, Universitaetsstrasse. 31, 93040 Regensburg, Germany.
2
Institute of Medical Microbiology and Hygiene, University Regensburg.
3
Institute of Medical Microbiology and Hygiene, University Regensburg; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
4
Department of Pharmaceutical Technology, University Regensburg, Universitaetsstrasse. 31, 93040 Regensburg, Germany. Electronic address: miriam.breunig@chemie.uni-regensburg.de.

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 non-specific adsorption to SiNPs. Firstly, 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. Secondly, 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, while adsorbed Env resulted only in a moderate 1.4-fold increase compared to 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.

PMID:
31682830
DOI:
10.1016/j.xphs.2019.10.059

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