Prolonged delivery of HIV-1 vaccine nanoparticles from hydrogels

Raphael Mietzner; Clara Barbey; Heike Lehr; Christian E Ziegler; David Peterhoff; Ralf Wagner; Achim Goepferich; Miriam Breunig

doi:10.1016/j.ijpharm.2024.124131

Prolonged delivery of HIV-1 vaccine nanoparticles from hydrogels

Int J Pharm. 2024 Apr 21:657:124131. doi: 10.1016/j.ijpharm.2024.124131. Online ahead of print.

Authors

Raphael Mietzner¹, Clara Barbey¹, Heike Lehr¹, Christian E Ziegler¹, David Peterhoff², Ralf Wagner², Achim Goepferich¹, Miriam Breunig³

Affiliations

¹ Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany.
² Institute of Medical Microbiology and Hygiene, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
³ Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany. Electronic address: miriam.breunig@ur.de.

PMID: 38643811
DOI: 10.1016/j.ijpharm.2024.124131

Abstract

Immunization is a straightforward concept but remains for some pathogens like HIV-1 a challenge. Thus, new approaches towards increasing the efficacy of vaccines are required to turn the tide. There is increasing evidence that antigen exposure over several days to weeks induces a much stronger and more sustained immune response compared to traditional bolus injection, which usually leads to antigen elimination from the body within a couple of days. Therefore, we developed a poly(ethylene) glycol (PEG) hydrogel platform to investigate the principal feasibility of a sustained release of antigens to mimic natural infection kinetics. Eight-and four-armed PEG macromonomers of different MWs (10, 20, and 40 kDa) were end-group functionalized to allow for hydrogel formation via covalent cross-linking. An HIV-1 envelope (Env) antigen in its trimeric (Env_tri) or monomeric (Env_mono) form was applied. The soluble Env antigen was compared to a formulation of Env attached to silica nanoparticles (Env-SiNPs). The latter are known to have a higher immunogenicity compared to their soluble counterparts. Hydrogels were tunable regarding the rheological behavior allowing for different degradation times and release timeframes of Env-SiNPs over two to up to 50 days. Affinity measurements of the VCR01 antibody which specifically recognizes the CD4 binding site of Env, revealed that neither the integrity nor the functionality of Env_mono-SiNPs (K_d = 2.1 ± 0.9 nM) and Env_tri-SiNPs (K_d = 1.5 ± 1.3 nM), respectively, were impaired after release from the hydrogel (K_d before release: 2.1 ± 0.1 and 7.8 ± 5.3 nM, respectively). Finally, soluble Env and Env-SiNPs which are two physico-chemically distinct compounds, were co-delivered and shown to be sequentially released from one hydrogel which could be beneficial in terms of heterologous immunization or single dose vaccination. In summary, this study presents a tunable, versatile applicable, and effective delivery platform that could improve vaccination effectiveness also for other infectious diseases than HIV-1.

Keywords: Antigen PEGylation; Co-delivery; Env; HIV vaccine; PEG hydrogel; Silica nanoparticles; Sustained release.