title: A gold glyco-nanoparticle carrying a Listeriolysin O peptide and formulated with Advax™ delta inulin adjuvant induces robust T-cell protection against listeria infection.
abstract: 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.
authors: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors: Estela
authors: E
authors: Rodriguez-Del Rio
authors: CIC biomaGUNE, P° de Miramón 182, San Sebastian, Gipúzcoa, Spain; CIBER-BBN, P° de Miramón 182, San Sebastian, Gipúzcoa, Spain.
authors: Marco
authors: M
authors: Marradi
authors: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors: Ricardo
authors: R
authors: Calderon-Gonzalez
authors: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors: Elisabet
authors: E
authors: Frande-Cabanes
authors: CIC biomaGUNE, P° de Miramón 182, San Sebastian, Gipúzcoa, Spain; CIBER-BBN, P° de Miramón 182, San Sebastian, Gipúzcoa, Spain.
authors: Soledad
authors: S
authors: Penadés
authors: Department of Diabetes and Endocrinology, Flinders University, Adelaide 5042, SA, Australia; Vaxine Pty Ltd, Flinders Medical Centre, Adelaide 5042, SA, Australia.
authors: Nikolai
authors: N
authors: Petrovsky
authors: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain. Electronic address: calvarez@humv.es.
authors: Carmen
authors: C
authors: Alvarez-Dominguez
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006046:Gold; D006360:Heat-Shock Proteins / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology*; D007111:Immunity, Cellular; D007444:Inulin / Q000276:immunology; D007694:Killer Cells, Natural; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000517:prevention & control*; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D006046:Gold; D007444:Inulin; C038705:hlyA protein, Listeria monocytogenes
keywords: Advax; Dendritic cells; Glyconanoparticles; Listeriosis; Vaccines