Mietzner, Raphael and Barbey, Clara and Lehr, Heike and Ziegler, Christian E. and Peterhoff, David and Wagner, Ralf and Goepferich, Achim and Breunig, Miriam (2024) Prolonged delivery of HIV-1 vaccine nanoparticles from hydrogels. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 657: 124131. ISSN 0378-5173, 1873-3476
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONTROLLED ANTIBODY RELEASE; DIELS-ALDER HYDROGELS; SILICA NANOPARTICLES; ENVELOPE TRIMERS; ANTIGEN; PROTEIN; PEG; SIZE; CONJUGATION; STABILITY; HIV vaccine; PEG hydrogel; Sustained release; Silica nanoparticles; Env; Co-delivery; Antigen PEGylation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2025 06:40 |
| Last Modified: | 15 Jul 2025 06:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63500 |
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