title: Novel ISCOMs from Quillaja brasiliensis saponins induce mucosal and systemic antibody production, T-cell responses and improved antigen uptake.
abstract: In the last decades, significant efforts have been dedicated to the search for novel vaccine adjuvants. In this regard, saponins and its formulations as "immunostimulating complexes" (ISCOMs) have shown to be capable of stimulating potent humoral and cellular immune responses, enhanced cytokine production and activation of cytotoxic T cells. The immunological activity of ISCOMs formulated with a saponin fraction extracted from Quillaja brasiliensis (QB-90 fraction) as an alternative to classical ISCOMs based on Quil A(®) (IQA) is presented here. The ISCOMs prepared with QB-90, named IQB-90, typically consist of 40-50 nm, spherical, cage-like particles, built up by QB-90, cholesterol, phospholipids and antigen (ovalbumin, OVA). These nanoparticles were efficiently uptaken in vitro by murine bone marrow-derived dendritic cells. Subcutaneously inoculated IQB-90 induced strong serum antibody responses encompassing specific IgG1 and IgG2a, robust DTH reactions, significant T cell proliferation and increases in Th1 (IFN-γ and IL-2) cytokine responses. Intranasally delivered IQB-90 elicited serum IgG and IgG1, and mucosal IgA responses at distal systemic sites (nasal passages, large intestine and vaginal lumen). These results indicate that IQB-90 is a promising alternative to classic ISCOMs as vaccine adjuvants, capable of enhancing humoral and cellular immunity to levels comparable to those induced by ISCOMs manufactured with Quillaja saponaria saponins.
authors.affiliation: FEPAGRO Saúde Animal, Instituto de Pesquisas Veterinárias Desidério Finamor, Laboratório de Virologia, Eldorado do Sul, RS, Brazil; Departamento de Microbiologia Imunologia e Parasitologia, Laboratório de Virologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Samuel Paulo
authors.initials: SP
authors.lastname: Cibulski
authors.affiliation: Cátedra de Inmunología, Departamento de Biociencias, Facultad de Ciencias/Química, Universidad de la República (UdelaR), Av. Alfredo Navarro 3051, Montevideo CP. 11600, Uruguay.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mourglia-Ettlin
authors.affiliation: FEPAGRO Saúde Animal, Instituto de Pesquisas Veterinárias Desidério Finamor, Laboratório de Virologia, Eldorado do Sul, RS, Brazil.
authors.forename: Thais Fumaco
authors.initials: TF
authors.lastname: Teixeira
authors.affiliation: Laboratorio de Carbohidratos y Glicoconjugados, Departamento de Desarrollo Biotecnológico, Facultad de Medicina. Universidad de la República (UdelaR), Av. Alfredo Navarro 3051, Montevideo CP. 11600, Uruguay.
authors.forename: Lenora
authors.initials: L
authors.lastname: Quirici
authors.affiliation: Departamento de Microbiologia Imunologia e Parasitologia, Laboratório de Virologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Paulo Michel
authors.initials: PM
authors.lastname: Roehe
authors.affiliation: Laboratorio de Carbohidratos y Glicoconjugados, Departamento de Desarrollo Biotecnológico, Facultad de Medicina, Departamento de Química Orgánica, Facultad de Química, Universidad de la República (UdelaR), Av. Alfredo Navarro 3051, Montevideo CP. 11600, Uruguay.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ferreira
authors.affiliation: Laboratorio de Carbohidratos y Glicoconjugados, Departamento de Desarrollo Biotecnológico, Facultad de Medicina. Universidad de la República (UdelaR), Av. Alfredo Navarro 3051, Montevideo CP. 11600, Uruguay. Electronic address: fsilveir@higiene.edu.uy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Silveira
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016882:ISCOMs / Q000737:chemistry / Q000494:pharmacology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D031990:Quillaja / Q000737:chemistry; D062605:Quillaja Saponins / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014709:Vero Cells
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D016882:ISCOMs; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C570176:QB 90U; D062605:Quillaja Saponins; D012503:Saponins; C046386:Quil A
keywords: Humoral and cell responses; ISCOM; Intranasally delivered; Quillaja brasiliensis; Subcutaneously; Uptake