A gold glyco-nanoparticle carrying a Listeriolysin O peptide and formulated with Advax™ delta inulin adjuvant induces robust T-cell protection against listeria infection

Vaccine. 2015 Mar 17;33(12):1465-73. doi: 10.1016/j.vaccine.2015.01.062. Epub 2015 Feb 7.


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.

Keywords: Advax; Dendritic cells; Glyconanoparticles; Listeriosis; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Bacterial Toxins / immunology*
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Gold
  • Heat-Shock Proteins / immunology*
  • Hemolysin Proteins / immunology*
  • Immunity, Cellular
  • Inulin / immunology
  • Killer Cells, Natural
  • Listeria monocytogenes / immunology*
  • Listeriosis / prevention & control*
  • Metal Nanoparticles*
  • Mice
  • Mice, Inbred BALB C
  • Spleen / cytology
  • T-Lymphocytes / immunology*
  • Vaccination


  • Adjuvants, Immunologic
  • Bacterial Toxins
  • Bacterial Vaccines
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Gold
  • Inulin
  • hlyA protein, Listeria monocytogenes