title: Adjuvant activity of CpG-ODN formulated as a liquid crystal.
abstract: The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase I-III clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O-ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)3. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C(high) monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co-injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines.
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Sánchez Vallecillo
authors.affiliation: Departamento de Farmacia, UNITEFA (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Ullio Gamboa
authors.affiliation: Departamento de Farmacia, UNITEFA (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: Santiago D
authors.initials: SD
authors.lastname: Palma
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Harman
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Chiodetti
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Morón
authors.affiliation: Departamento de Farmacia, UNITEFA (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Allemandi
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Pistoresi-Palencia
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina. Electronic address: belkys@fcq.unc.edu.ar.
authors.forename: Belkys A
authors.initials: BA
authors.lastname: Maletto
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000493:pharmacokinetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000941:Antigens / Q000276:immunology; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D001219:Aspartate Aminotransferases / Q000097:blood; D001682:Biological Availability; D002478:Cells, Cultured; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D050866:Liquid Crystals / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000493:pharmacokinetics*; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014612:Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014612:Vaccines; D010047:Ovalbumin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid
keywords: Adjuvant; Ascorbyl palmitate; CpG-ODN; Liquid crystal; Vaccine