Melt Processing Virus-Like Particle-Based Vaccine Candidates into Biodegradable Polymer Implants.

Autor: Puente AA; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA., Ortega-Rivera OA; Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA.; Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, CA, USA., Wirth DM; Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA., Pokorski JK; Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA.; Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, CA, USA.; Institute for Materials Design and Delivery, University of California San Diego, La Jolla, CA, USA., Steinmetz NF; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.; Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.; Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.; Institute for Materials Design and Delivery, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.; Department of Radiology, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.; Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. nsteinmetz@eng.ucsd.edu.
Jazyk: angličtina
Zdroj: Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2024; Vol. 2720, pp. 221-245.
DOI: 10.1007/978-1-0716-3469-1_16
Abstrakt: Melt processing is an emerging production method to efficiently encapsulate proteins into polymeric devices for sustained release. In the context of vaccines, melt processing is well-suited to develop vaccine delivery devices that are stable outside the cold chain and can generate protective immunity from a single dose. We have demonstrated the compatibility of bacteriophage Qβ virus-like particles (VLPs) with hot-melt extrusion (HME) and have leveraged this technology to develop a single-dose vaccine candidate for vaccination against human papillomavirus (HPV). Here, we detail the methods for chemically conjugating an HPV peptide epitope from the L2 minor capsid protein to Qβ VLPs to generate HPV-Qβ particles. We outline techniques used to characterize HPV-Qβ particles, and we elaborate on the process to encapsulate HPV-Qβ into biodegradable poly(lactic-co-glycolic acid) (PLGA) implants and discuss methods for the materials characterization of the HPV-Qβ/polymer melts. The methods described could be adapted to other disease targets, i.e., by conjugation of a different peptide epitope, or transferred to other VLP systems suited for conjugation, immune response, or stability during processing. Such VLPs are ideally suited for use in HME, a mature, scalable, continuous, and solvent-free process which can be adapted to mold devices, therefore allowing the processing of the melts into various geometries, such as subcutaneous implants, or self-administrable microneedle patches.
(© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE