Novel ISCOMs from Quillaja brasiliensis saponins induce mucosal and systemic antibody production, T-cell responses and improved antigen uptake

被引:49
作者
Cibulski, Samuel Paulo [1 ,2 ]
Mourglia-Ettlin, Gustavo [3 ]
Teixeira, Thais Fumaco [1 ]
Quirici, Lenora [4 ]
Roehe, Paulo Michel [2 ]
Ferreira, Fernando [5 ]
Silveira, Fernando [4 ]
机构
[1] FEPAGRO Saude Anim, Inst Pesquisas Vet Desiderio Finamor, Lab Virol, Eldorado Do Sul, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Lab Virol, Dept Microbiol Imunol & Parasitol, Porto Alegre, RS, Brazil
[3] Univ Republ UdelaR, Fac Ciencias Quim, Dept Biociencias, Catedra Inmunol, Av Alfredo Navarro 3051, Montevideo 11600, Uruguay
[4] Univ Republ UdelaR, Fac Med, Dept Desarrollo Biotecnol, Lab Carbohidratos & Glicoconjugados, Av Alfredo Navarro 3051, Montevideo 11600, Uruguay
[5] Univ Republ UdelaR, Fac Quim, Lab Carbohidratos & Glicoconjugados, Dept Desarrollo Biotecnol,Fac Med,Dept Quim Organ, Av Alfredo Navarro 3051, Montevideo 11600, Uruguay
关键词
Quillaja brasiliensis; ISCOM; Uptake; Subcutaneously; Intranasally delivered; Humoral and cell responses; ADJUVANT FORMULATIONS; THERAPEUTIC VACCINES; DELIVERY; ISCOMATRIX; GENERATION; STRATEGIES;
D O I
10.1016/j.vaccine.2016.01.029
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (R) (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-gamma 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. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1162 / 1171
页数:10
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