The Investigation and Characterisation of Protein Nanocapsules as an Emerging Nanoparticle Vaccine Delivery System
Creators: name: Skakic, Ivana
Publisher: name: RMIT University
Year: 2025
Subjects: classificationCode: 320211
subject: Infectious diseases

description: Nanoparticle vaccines are a new class of vaccine formulation utilising submicron particles to deliver vaccine antigens. Nanoparticle vaccines vary in size, shape, composition, and immunogenic properties owing to the diversity of material and formulations available. Particles may be composed of inorganic material such as metal, silica, iron oxide or synthetic polymer, as well as organic materials such as protein, lipid or chitin. 
Nanoparticles in sub-micron size ranges of 50-500 nm are readily internalised by dendritic cells which play a key role in antigen processing and presentation, as well as development of strong immune responses and memory formation. The development of biodegradable and biocompatible nanoparticles has promise as a safe and effective vaccine platform to deliver vaccine antigens. 
Helicobacter pylori (H. pylori) is an important human pathogen which causes a significant global health burden, infecting an estimated 50% of the global population. Increasing rates of antibiotic resistance have increased efforts towards a viable vaccine against H. pylori. Known antigens such as Urease are key vaccine targets in the development of a vaccine against H. pylori. 
In this study, the synthesis of protein ‘nanocapsules’ composed of pure cross-linked Urease subunit A (UreA) antigen was investigated for its potential as an effective vaccine against 
H. pylori. A templating system utilising two kinds of silica template (either solid-core mesoporous shell (SC/MS) or fully mesoporous (MS) nanoparticles) immobilises proteins in the mesoporous silica by solution adsorption. Crosslinking proteins in place followed by dissolution of silica template by acid treatment, pure antigen based nanocapsules were synthesised. Previous studies utilising the SC/MS nanoparticle templating system found that antigen nanocapsules were successfully delivered to intracellular compartments in murine dendritic cells (Taki et al., 2020).
Recombinant UreA protein was expressed through a bacterial expression system and purified before infiltration and nanocapsule synthesis. Resulting nanocapsules were characterised structurally and investigated for cytotoxicity and cell uptake in vitro before being assessed as a novel vaccine in mice.
The results of a preliminary mouse trial indicated the efficacy of the SC/MS and MS protein nanocapsules as a vaccine delivery system and were used as the basis for the development of a novel HIV vaccine based on the gp120 antigen of HIV. Results from this study found that SC/MS nanocapsules were able to reduce H. pylori burden in mice, and that two distinct sizes of nanocapsule were successfully synthesised from the HIV protein gp120 indicating that the platform offers a versatile approach to protein delivery. The results of this study indicate that protein nanocapsules have potential to be an effective and immunogenic vaccine platform which can be used to effectively deliver antigen.