In vitro and in vivo Immunoadjuvant Effects of the Enzymatically Modified Fucoidan

T. Kuznetsova, T. Smolina, L. A. Ivanushko, E. V. Persiyanova, A. Silchenko, N. Besednova
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Abstract

Objectives. No sulfated polysaccharides (fucoidans) has been declared as the pharmaceutical substances, adjuvants, etc., which is associated with the problems of obtaining the structurally characterized and homogeneous samples or their oligomeric fractions that retain high biological activity. The highly purified fucoidan with regular reproducible structural characteristics (F1) was obtained by enzymatic hydrolysis of native fucoidan (F2). Aim. The comparative study of fucoidans from the brown alga Fucus evanescens (F1 and F2) effects on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA) in vitro and in vivo. Material and methods. Fucoidan F1 — the enzymatically modified product of native fucoidan; F2 — the native fucoidan. The fucoidans effects on the expression level of the main immunophenotypic markers of innate and adaptive immunity (neutrophils, monocytes, natural killers, lymphocytes) cells in vitro were studied by methods of flow cytometry. The fucoidans effects on the production of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFNγ, IL-2, IL-10, IL-12) were detected in BALB/c mice immunized with OVA. Results. The tested fucoidans activate the effector functions of innate and adaptive immunity cells loaded with OVA in vitro and act as adjuvants, stimulating both Th1 (IgG2а, INFγ, IL-2) and Th2 (IgG1, IL-10) immune response to OVA in vivo. Conclusions. The immunoadjuvant effect of the enzymatically modified fucoidan (F1) on effector functions of innate and adaptive immunity cells are comparable to those of the native fucoidan (F2). The findings determine the possibility of F1 use as an adjuvant for a wide range of prophylactic and therapeutic vaccines.
酶修饰岩藻糖聚糖的体外和体内免疫佐剂作用
目标。没有硫酸酸化多糖(岩藻多糖)被宣布为药物物质、佐剂等,这与获得结构表征和均匀的样品或其低聚组分保持高生物活性的问题有关。通过酶解天然岩藻糖聚糖(F2)获得了具有规则可重复结构特征的高纯度岩藻糖聚糖(F1)。的目标。褐藻褐藻多糖(F1和F2)对携带卵清蛋白(OVA)的先天免疫细胞和适应性免疫细胞效应功能的体外和体内比较研究。材料和方法。岩藻糖聚糖F1 -天然岩藻糖聚糖的酶修饰产物;F2 -天然岩藻聚糖。采用流式细胞术研究岩藻胶对体外天然免疫和适应性免疫主要免疫表型标志物(中性粒细胞、单核细胞、自然杀伤细胞、淋巴细胞)表达水平的影响。检测岩藻多糖对OVA免疫BALB/c小鼠血清中OVA特异性抗体(IgG、IgG1、igg2)和细胞因子(IFNγ、IL-2、IL-10、IL-12)产生的影响。结果。在体外实验中,这些岩藻多糖激活了承载OVA的先天免疫细胞和适应性免疫细胞的效应功能,并作为佐剂,在体内刺激Th1 (igg2, INFγ, IL-2)和Th2 (IgG1, IL-10)对OVA的免疫应答。结论。酶修饰的岩藻糖聚糖(F1)对先天和适应性免疫细胞效应功能的免疫佐剂作用与天然岩藻糖聚糖(F2)相当。这些发现确定了F1作为广泛的预防性和治疗性疫苗的佐剂的可能性。
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