Specific immune response to HBsAg is enhanced by β-glucan oligosaccharide containing an α-(1 → 3)-linked bond and biased towards M2/Th2
Specific immune response to HBsAg is enhanced by β-glucan oligosaccharide containing an α-(1 → 3)-linked bond and biased towards M2/Th2
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DOI：
10.1016/j.intimp.2007.01.004
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发表时间：
2007-06-01
影响因子：
5.6
通讯作者：
Qu, Di
中科院分区：
文献类型：
--
作者：
Dong, Sheng-Fu;Chen, Jie-Min;Qu, Di
接种B型肝炎表面抗原（HBsAg）疫苗可预防HBV感染。10%的疫苗接种者未能产生保护性抗体，这一事实促进了对更有效的疫苗接种策略的大量研究。β-（1 -> 6）-支链-（1 -> 3）葡六糖是香菇多糖和其他几种具有免疫刺激活性的真菌β-葡聚糖的基本单元。β-葡聚糖主要通过与骨髓细胞（巨噬细胞）和树突状细胞的相互作用来刺激先天性免疫应答。在本研究中，已经评估了合成的β-（1 -> 6）-分支的β-（1 -> 3）葡糖六糖类似物（β-> 6）增强对HBsAg的免疫应答的能力。与单独抗原相比，在BALB/c小鼠中i. p.给予合成β-glu 6大大增强了巨噬细胞和树突状细胞对共同给予HBsAg的动员和成熟。根据脾脏中CD 69阳性CD 4（+）和CD 19（+）淋巴细胞的百分比判断，β-glu 6的佐剂效应在对HBsAg应答的T和B细胞活化增加方面是明显的。β-glu 6可显著增加对HBsAg应答的IL-4产生细胞的数量，而对IFN-γ产生淋巴细胞的数量没有影响，表明免疫应答的Th 2偏好。通过使用β-glu 6作为疫苗佐剂，HBV疫苗接种保护的相关性，即HBsAg特异性抗体的滴度大大增强。在用HBsAg加β-glu 6免疫的小鼠中，抗HBsAg抗体内的IgG 1/IgG 2a比率高于仅接受HBsAg或给予HBsAg与弗氏佐剂的小鼠，表明向Th 2偏向的抗炎保护性抗体应答转变。(C)2007 Elsevier B. V.保留所有权利。
Vaccination with Hepatitis B surface antigen (HBsAg) is being used to prevent HBV infection. The fact that 10% of vaccinees fail to develop protective antibodies has fostered a large body of research for more effective vaccination strategies. Search for new adjuvant, able to selectively trigger protective antibody production, is one of the most promising approaches.The oligosaccharide beta-(1 -> 6)-branched-(1 -> 3) glucohexaose is the basic unit of lentinan and several other fungal beta-glucans with immunostimulatory activity. beta-glucans stimulate innate immune response mainly through interaction with myeloid cells (macrophages) and dendritic cells.In this study, the ability of synthetic beta-(1 -> 6)-branched beta-(1 -> 3) glucohexaose analogue (beta -> 6) to enhance the immune response to HBsAg has been evaluated. Administration of synthetic beta-glu6 i.p. in BALB/c mice greatly enhanced the mobilisation and maturation of macrophages and dendritic cells to co-administered HBsAg, as compared to the antigen alone. The adjuvant effect of beta-glu6 was evident in the increase of T and B cell activation in response to HBsAg, as judged by the percentage of CD69-positive CD4(+) and CD19(+) lymphocytes in the spleen. beta-glu6 could significantly enhance the number of IL-4-producing cells in response to HBsAg, while it had no effect on the number of IFN-gamma-producing lymphocytes, suggesting a Th2 bias of the immune response. The correlate of protection for HBV vaccination, i.e. the titer of HBsAg-specific antibodies, was greatly enhanced by the use of beta-glu6 as a vaccine adjuvant. The IgG1/IgG2a ratio within the anti-HBsAg antibodies was higher in the mice immunised with HBsAg plus beta-glu6 than receiving HBsAg alone or mice administered HBsAg with Freund's adjuvant, indicating a shift towards a Th2-biased anti-inflammatory protective antibody response. (C) 2007 Elsevier B.V. All rights reserved.