TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8+ T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice. Collectively, these data reveal the potential utility of chimeric adjuvants with synergistic activities mediated via TLRs.
Author Info: (1) InvivoGen, 31400 Toulouse, France. Laboratoire de Biologie Tissulaire et d'Ingenierie Therapeutique, UMR5305, Universite Lyon 1, CNRS, 69007 Lyon, France. Groupe Immunite des M
Author Info: (1) InvivoGen, 31400 Toulouse, France. Laboratoire de Biologie Tissulaire et d'Ingenierie Therapeutique, UMR5305, Universite Lyon 1, CNRS, 69007 Lyon, France. Groupe Immunite des Muqueuses et Agents Pathogenes, Faculte de Medecine de Saint-Etienne, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, 42023 Saint-Etienne, France. (2) Sorbonne Universites, Universite Pierre et Marie Curie - Universite Paris VI, Departement Hospitalo-Universitaire "Vieillissement Immunitaire et Stress," Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. (3) Sorbonne Universites, Universite Pierre et Marie Curie - Universite Paris VI, Departement Hospitalo-Universitaire "Vieillissement Immunitaire et Stress," Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. (4) InvivoGen, 31400 Toulouse, France. (5) InvivoGen, 31400 Toulouse, France. (6) InvivoGen, 31400 Toulouse, France. (7) Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; and. (8) Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; and. (9) InvivoGen, 31400 Toulouse, France. (10) InvivoGen, 31400 Toulouse, France. (11) Sorbonne Universites, Universite Pierre et Marie Curie - Universite Paris VI, Departement Hospitalo-Universitaire "Vieillissement Immunitaire et Stress," Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses, 75252 Paris, France. International Research Center of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan. (12) Laboratoire de Biologie Tissulaire et d'Ingenierie Therapeutique, UMR5305, Universite Lyon 1, CNRS, 69007 Lyon, France. (13) Groupe Immunite des Muqueuses et Agents Pathogenes, Faculte de Medecine de Saint-Etienne, INSERM Centre d'Investigation Clinique en Vaccinologie 1408, 42023 Saint-Etienne, France; stephane.paul@chu-st-etienne.fr.
