In the search for an effective
vaccine against the human pathogen, Listeria monocytogenes (Listeria),
gold glyconanoparticles (GNP) loaded with a
listeriolysin O peptide LLO91-99 (GNP-LLO) were used to immunise mice, initially using a dendritic cell (DC)
vaccine approach, but subsequently using a standard parenteral immunisation approach. To enhance vaccine immunogenicity a novel
polysaccharide adjuvant based on
delta inulin (Advax™) was also co-formulated with the GNP
vaccine. Confirming previous results, DC loaded in vitro with GNP-LLO provided better protection against
listeriosis than DC loaded in vitro using free LLO
peptide. The immunogenicity of GNP-LLO loaded DC
vaccines was further increased by addition of Advax™ adjuvant. However, as DC
vaccines are expensive and impracticable for prophylactic use, we next asked whether the same GNP-LLO
antigen could be used to directly target DC in vivo. Immunisation of mice with GNP-LLO plus Advax™ adjuvant induced LLO-specific T-cell immunity and protection against Listeria challenge. Protection correlated with an increased frequency of splenic CD4(+) and CD8(+) T cells, NK cells and CD8α(+) DC, and Th1
cytokine production (IL-12, IFN-γ, TNF-α, and MCP-1), post-challenge. Enhanced
T-cell epitope recruitment post-challenge was seen in the groups that received Advax™ adjuvant. Immunisation with GNP-LLO91-99 plus Advax™ adjuvant provided equally robust Listeria protection as the best DC
vaccine strategy but without the complexity and cost, making this a highly promising strategy for development of a prophylactic
vaccine against
listeriosis.