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

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..

Medienart:

Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:33

Enthalten in:

Vaccine - 33(2015), 12, Seite 1465-1473

Sprache:

Englisch

Beteiligte Personen:

Rodriguez-Del Rio, Estela [VerfasserIn]
Marradi, Marco [Sonstige Person]
Calderon-Gonzalez, Ricardo [Sonstige Person]
Frande-Cabanes, Elisabet [Sonstige Person]
Penadés, Soledad [Sonstige Person]
Petrovsky, Nikolai [Sonstige Person]
Alvarez-Dominguez, Carmen [Sonstige Person]

Links:

Volltext
www.ncbi.nlm.nih.gov
search.proquest.com

Themen:

APC
Abbreviations
Antigen-presenting cells
Apoptosis
Bacterial Toxins - immunology
Bacterial Vaccines - immunology
Biocompatibility
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
CFU
Cathepsin-D
Colony forming units
Ctsd
Cytokines - immunology
Cytokines - metabolism
Dendritic Cells - immunology
Dendritic cells
Epitopes, T-Lymphocyte - immunology
GNP
Glucose
Gold glyconanoparticles
Heat-Shock Proteins - immunology
Hemolysin Proteins - immunology
Hepatitis
I.p
I.v
Intra-peritoneal
Intra-venous
Inulin - immunology
LLO
Ligands
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Listeriolysin O
Listeriosis - prevention & control
Lymphocytes
MHC
MHC-class II antigen loading compartments
MIIC
Macrophages
Major histocompatibility complex
Peptides
Spleen - cytology
T cell receptors
T-Lymphocytes - immunology
Vaccines
West Nile virus

doi:

10.1016/j.vaccine.2015.01.062

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC195670650X