The member of the cyclic di-nucleotide family bis-(3′, 5′)-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant
The member of the cyclic di-nucleotide family bis-(3′, 5′)-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant
复制标题
DOI：
10.1016/j.vaccine.2009.12.045
复制
发表时间：
2010-03-02
期刊：
影响因子：
5.5
通讯作者：
Guzman, Carlos A.
中科院分区：
文献类型：
--
作者：
Libanova, Rimma;Ebensen, Thomas;Guzman, Carlos A.
在这里，我们证明了双-（3 '，5'）-环状二聚肌苷一磷酸（c-di-IMP）表现出有效的佐剂特性。BALB/c或C57 BL/6小鼠通过鼻内途径用模型抗原β-半乳糖苷酶（β-Gal）或卵清蛋白（OVA）单独或与c-di-IMP共同给药免疫。接受c-di-IMP的动物显示血清中的抗β-Gal或OVA免疫球蛋白G滴度（IgG）显著高于仅接种P-Gal或OVA的动物。此外，在不同的粘膜区域中也可检测到强的局部免疫应答，如高水平的β-Gal特异性分泌伊加（slgA）所示。血清中抗原特异性IgG同种型的分析，以及免疫动物淋巴细胞分泌的细胞因子和趋化因子的谱显示，使用c-di-IMP导致刺激混合T（H）1/T（H）2/T（H）17应答。使用c-di-IMP作为佐剂用OVA对C57 BL/6小鼠进行粘液素免疫也导致体液和细胞的刺激（即，60%的抗原特异性裂解）应答。我们的研究结果表明，新化合物c-di-IMP与抗原通过粘膜途径共同给药时，表现出很强的佐剂特性，从而代表了一种有前途的候选佐剂，用于粘膜疫苗接种策略的发展。(C)2009爱思唯尔有限公司保留所有权利。
Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP showed significantly higher anti-beta-Gal or OVA immunoglobulin G titres (IgG) in sera than those vaccinated with P-Gal or OVA alone. Furthermore, strong local immune responses were also detectable in different mucosal territories, as shown by the high levels of beta-Gal-specific secretory IgA (slgA). The analysis of the antigen-specific IgG isotypes in sera, together with the profiles of the cytokines and chemokines secreted by lymphocytes from vaccinated animals showed that the use of c-di-IMP resulted in stimulation of a mixed T(H)1/T(H)2/T(H)17 response. Mucosal immunization of C57BL/6 mice with OVA using c-di-IMP as adjuvant also led to the stimulation of both humoral and cellular (i.e., 60% of antigen-specific lysis by in vivo CTL) responses. Our results demonstrated that the novel compound c-di-IMP exhibits strong adjuvant properties when co-administered with an antigen by the mucosal route, thereby representing a promising candidate adjuvant for the development of mucosal vaccination strategies. (C) 2009 Elsevier Ltd. All rights reserved.