Cutting edge: New chimeric NOD2/TLR2 adjuvant drastically increases vaccine immunogenicity.
TLR ligands are critical activators of innate immunity and are being developed as vaccine adjuvants. However, their usefulness in conjunction with NOD-like receptor agonists remains poorly studied. In this study, we evaluated a new ligand that targets both TLR2 and NOD2 receptors. We assessed its ability to enhance dendritic cell maturation in vitro in addition to improving systemic and mucosal immune responses in mice. The chimeric NOD2/TLR2 ligand induced synergistic upregulation of dendritic cell maturation markers, costimulatory molecules, and secretion of proinflammatory cytokines compared with combinations of separate ligands. Furthermore, when coadministered with biodegradable nanoparticles carrying a model Ag, the ligand was able to induce high Ag-specific IgA and IgG titers at both systemic and mucosal sites after parenteral immunizations. These findings point out the potential utility of chimeric molecules TLR/NOD as adjuvants for vaccines to induce systemic and mucosal immune responses.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5305, Université de Lyon, Lyon F-69007, France; Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon, Saint-Etienne F-42023, France; and.
Vincent
V
Pavot
Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon, Saint-Etienne F-42023, France; and.
Nicolas
N
Rochereau
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5305, Université de Lyon, Lyon F-69007, France;
Julien
J
Rességuier
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5305, Université de Lyon, Lyon F-69007, France; Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon, Saint-Etienne F-42023, France; and Cayla-InvivoGen, Toulouse F-31000, France.
Alice
A
Gutjahr
Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon, Saint-Etienne F-42023, France; and.
Christian
C
Genin
Cayla-InvivoGen, Toulouse F-31000, France.
Gerard
G
Tiraby
Cayla-InvivoGen, Toulouse F-31000, France.
Eric
E
Perouzel
Cayla-InvivoGen, Toulouse F-31000, France.
Thierry
T
Lioux
Cayla-InvivoGen, Toulouse F-31000, France.
Fabienne
F
Vernejoul
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5305, Université de Lyon, Lyon F-69007, France;
Bernard
B
Verrier
Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, Université de Lyon, Saint-Etienne F-42023, France; and stephane.paul@chu-st-etienne.fr.
Stéphane
S
Paul
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008024:Ligands; D055666:Lipopeptides / Q000235:genetics / Q000276:immunology; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D010641:Phenotype; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014612:Vaccines / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D016207:Cytokines; D016655:HIV Core Protein p24; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008024:Ligands; D055666:Lipopeptides; D053473:Nod2 Signaling Adaptor Protein; D051195:Toll-Like Receptor 2; D014612:Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide