A new approach to antigen delivery using nanoparticle templating system

摘要

Vaccines are invaluable factors in our current health system for preventing pathogenic infection. However, traditional vaccines have been unsuccessful in preventing against some important infections, such as malaria, HIV and hepatitis C. Although many potential antigens have been discovered, the lack of universal protection may be due to the inability of conventional delivery methods to elicit the immune responses appropriate for a particular infectious agent. Most of the protein subunit vaccines primarily induce antibody-mediated humoral responses; therefore, there is an urgent need for a new delivery method that delivers antigen to also elicit more potent antigen-specific cellular responses. Utilising nanotechnology in the field of medicine has gained pace in recent years. Nanoparticles such as silica, liposomes and more recently synthetic polymer particles, have been developed as vaccine/drug carriers and many are being studied comprehensively as promising candidates. These nanoparticle vehicles have been demonstrated to be efficiently taken up by dendritic cells, one of the most important cells which controls the fate of an antigen-specific immune response. These particles therefore have the ability to induce strong humoral and cellular responses. However, there have been no reports of a vaccine delivery system based on the preparation of nanoparticles derived from antigen only using a template, which would alleviate some of the disadvantages of existing nanoparticles. Through a templating system using silica nano-sized particles, proteins can be immobilised in the mesoporous shell by solution adsorption. This simple-step preparation of antigen nanoparticles has the potential to develop new generation vaccines against currently unpreventable infectious diseases. In this study, solid core mesoporous shell (SC/MS) silica nanoparticles averaging 410 nm in diameter were fabricated as a template for the subsequent synthesis of protein-based nanocapsules, employing ovalbumin as a model protein. Firstly, the ovalbumin-based nanocapsules of approximately 500 nm were successfully taken up by murine immature dendritic cells, and processed peptides were presented on MHC class I molecules, required for the activation of cytotoxic T cells. Secondly, a murine malarial protein, the merozoite surface protein 4/5 from Plasmodium chabaudi adami was used to synthesise nanocapsules using the templating system, and shown to elicit both humoral and cellular responses in immunised mice. These results highlight the potential of antigen-based nanocapsules, prepared from the nanoparticle templating system, for antigen delivery.