Nanoparticle HIV vaccines
No safe HIV vaccines have been able to stimulate durable, activated T-cell immunity. We are investigating an exciting HIV vaccination approach using hollow, submicron, delivery vehicles (nanocapsules) assembled using layer-by-layer technology. This is a novel, cross-disciplinary project with the Caruso group at University of Melbourne. Nanocapsules are designed to induce optimal immune responses by protecting antigens from degradation prior to reaching sites of immune activation and activate antigen presenting cells in a way that will initiate anti-viral immune responses. We aim to use controlled-release nanocapsules to stimulate durable CD4 and CD8 T cell responses in vivo.
Our work 94,108,110 * has shown that nanoparticles are efficiently endocytosed by dendritic cells and monocytes in fresh whole blood in a dose dependent manner. Furthermore, we have assembled nanocapsules containing an SIV Gag peptide KP9 and demonstrated that when KP9-nanocapsules are incubated with blood from positive macaque, KP9-specific T cells are stimulated to secrete cytokines. 94 *
These exciting initial findings have been achieved with standard nanoparticles prepared from a range of different polymers that are simple in design and can be prepared rapidly. We are now testing these nanocapsules HIV vaccines in animal models. Further, we are utilising the enormous flexibility of this approach to incorporate novel adjuvants to improve the immunogenicity of these vaccines. In addition, we are also investigating the use of these particles to target anti-HIV inhibitory RNAs to HIV-infected CD4 T cells as a therapeutic strategy. As part of this strategy we have been investigating novel ways to avoid non-specific uptake of particles - so called "stealth" particles. Recent work in this area can be found here. 201,210,232,235 *
* superscript number links to a specific publication in the chronological listing on Stephen's blog
Professor Stephen Kent, Dr Adam Wheatley, Ms Sheilajen Alcantara, Dr Hyon-Xhi Tan in collaboration with Prof Frank Caruso (Univ Melbourne Engineering), Dr Angus Johnston (at Monash Pharmacy in Parkville), and other collaborators within the ARC Centre of Excellence in CBNS.
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