title: Directing vaccine immune responses to mucosa by nanosized particulate carriers encapsulating NOD ligands.
abstract: Mucosal surfaces are a major portal of entry for many pathogens that are the cause of infectious diseases. Therefore, effective vaccines that induce a protective immune response at these sites are much needed. However, despite early success with the live attenuated oral polio vaccine over 50 years ago, only a few new mucosal vaccines have been subsequently licensed. Development of new adjuvants, comprising antigen delivery platforms and immunostimulatory molecules, are critical for the successful development of new mucosal vaccines. Among them, biodegradable nanoparticle delivery systems are promising and NOD-like receptors are considered as potential new targets for immunostimulatory molecules. In this work, different NOD1 and NOD2 ligands were encapsulated in polylactic acid (PLA) nanoparticles, coated with HIV-1 gag p24 antigen. We showed that these new formulations are able to induce proliferation of HIV-specific T cells from HIV(+) individuals as well as autophagy. In vivo, these formulations highly enhanced p24-specific systemic and mucosal immune responses in mice not only after mucosal administration but also after immunization via the parenteral route. Our results provide a rational approach for combining nanosized particulate carriers and encapsulated NOD receptor ligands as potent synergistic tools for induction of specific mucosal immunity.
authors.affiliation: Laboratoire de Biologie Tissulaire et d'Ingénierie Thrérapeutique, IBCP, Université Lyon 1, CNRS, UMR 5305, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pavot
authors.affiliation: Hospital Clinic-IDIBAPS, HIVACAT, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Climent
authors.affiliation: Groupe Immunité des Muqueuses et Agents Pathogènes - INSERM CIC1408 Vaccinologie, Faculté de Médecine de Saint-Etienne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rochereau
authors.affiliation: Hospital Clinic-IDIBAPS, HIVACAT, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.affiliation: Groupe Immunité des Muqueuses et Agents Pathogènes - INSERM CIC1408 Vaccinologie, Faculté de Médecine de Saint-Etienne, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.affiliation: InvivoGen, Toulouse, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Tiraby
authors.affiliation: InvivoGen, Toulouse, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Vernejoul
authors.affiliation: InvivoGen, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Perouzel
authors.affiliation: InvivoGen, Toulouse, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lioux
authors.affiliation: Laboratoire de Biologie Tissulaire et d'Ingénierie Thrérapeutique, IBCP, Université Lyon 1, CNRS, UMR 5305, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: Groupe Immunité des Muqueuses et Agents Pathogènes - INSERM CIC1408 Vaccinologie, Faculté de Médecine de Saint-Etienne, France. Electronic address: stephane.paul@univ-st-etienne.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Paul
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007109:Immunity; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D014611:Vaccination; D014621:Vagina
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008024:Ligands; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Adjuvant; Dendritic cells; Mucosa; NOD ligands; PLA nanoparticles; Vaccine formulations