Poster Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

Advancing vaccine research with biologically assembled biopolymers (#102)

Devi Jenika 1 , Saranya Pounraj 2 , David Wibowo 2 , Bernd H.A. Rehm 2 3 , 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
  3. Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia

Biopolymers have been investigated for their use as vaccine carriers due to their flexibility and effectiveness in inducing immune response. We explored the potential of bacterially assembled biopolymer particles (BP) made of polyhydroxybutyrate (PHB) as vaccine. After subcutaneous BP vaccination, C57BL/6 mice show no change in the number of innate and adaptive immune cells in the draining lymph nodes, but a temporary increase in TNF-a, MCP-1 and IL-6 is observed 16-hours post-injection. Next, we genetically engineered BP to express model antigen ovalbumin (BP-OVA) to further assess its antigen presenting capacity. Primary DCs are shown to present OVA-associated antigens to OVA-specific CD8+ and CD4+ T cells in vitro and in vivo. Subsequently, we found that subcutaneous vaccination of BP-OVA induces potent cytotoxic T cell (CTL) response in absence of CD4+ T cells help, as shown after detection of non-significant change of cytotoxic activity in vaccinated IAb-/- and CD40-/- mice compared to wild-type mice. Neither is conventional DCs type I (cDC1) required for BP-OVA CTL response, as shown by no change of CTL response in Batf3-/- mice. Subsequently, PolyI:C improves BP-OVA generated CTL response significantly, where CpG and lipopolysaccharide have failed to do so. Lastly, vaccination with BP-OVA show protective responses against B16-OVA melanoma and Em-myc-GFP lymphoma inoculation in vivo as shown by reduction of tumour nodules and tumour number respectively. In summary, we have characterised the immunogenicity of BP as vaccine carrier and demonstrated its effectiveness against tumour cells.