Poster Presentation Lorne Infection and Immunity 2020

Using nanoparticles as vaccine delivery carrier (#151)

Devi Jenika 1 , David Wibowo 2 , Bernd Rehm 2 , Justine Mintern 1
  1. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia
  2. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia

Nanoparticles have been shown to be an effective antigen-delivery carrier that induce a strong immune response. Polyhydroxyalkanoate (PHA) beads are produced by many archaea and bacteria and show promise as vaccines due to their flexibility, biodegradability and biocompatibility. PHA beads can be engineered to express many functional proteins on their surface, including antigens. Dendritic cells capture, process and present antigens to T cells. We have tested whether PHA beads can be used as a vaccine carrier using antigen presentation assays in vitro and in vivo. We have used in-vitro and in-vivo antigen presentation assays to determine whether dendritic cells capture and process antigen-associated PHA beads. Assays are conducted with PHA beads expressing peptide epitopes derived from the model antigen ovalbumin (OVA). Assays use OT-I and OT-II T cells that are specific for OVA257-264 and OVA323-339 epitope loaded into MHC I and MHC II, respectively. T cells are labelled with cell trace violet (CTV) which allows measurement of T cell division in response to antigen. Flow cytometry is used to measure T cell division by loss of the CTV dye. The data observed show T cells undergoing multiple cell divisions in-vitro after incubation with dendritic cells and PHA beads expressing OVA (OVA-PHA). Neither OT-I nor OT-II cells responded to OVA-PHA beads in the absence of dendritic cells. 0.1 mg OVA-PHA beads induced 1.5 fold higher OT-I division compare to the same dose of soluble OVA protein.  In contrast, the 0.1 mg OVA-PHA beads induced lower OT-II responses compared to soluble OVA alone.  In-vivo experiments were performed by adoptive transfer of OT-I and OT-II cells into mice that had previously received intravenous injection of OVA-PHA beads. 0.1 mg OVA-PHA beads were more effective in eliciting responses from OT-II compared to OT-I T cells. Overall, experiments suggest that OVA- PHA beads induce OVA-specific T cell divisions in vivo and in vitro. PHA beads are an effective vaccine carrier and can induce antigen specific T cell responses in vitro and following intravenous administration in vivo.