Immunogenicity and protective efficacy of rotavirus VP8fused to cholera toxin B subunit in a mouse model
Immunogenicity and protective efficacy of rotavirus VP8fused to cholera toxin B subunit in a mouse model
复制标题
霍乱毒素 B 亚基融合轮状病毒 VP8 在小鼠模型中的免疫原性和保护作用
DOI：
10.1080/21645515.2016.1204501
复制
发表时间：
2016
影响因子：
4.8
通讯作者：
Ningshao Xia
中科院分区：
文献类型：
--
作者：
Miaoge Xue;Linqi Yu;Lianzhi Jia;Yijian Li;Yuanjun Zeng;Tingdong Li;Shengxiang Ge;Ningshao Xia
在开发针对轮状病毒疾病的重组亚单位疫苗的尝试中，先前显示N-末端截短的VP 8 * 蛋白VP 8 -1（aa 26 -231）当与弗氏佐剂组合用于免疫时是良好的疫苗候选物。然而，当使用氢氧化铝作为佐剂时，该蛋白仅刺激弱的免疫应答。本研究利用霍乱毒素无毒B亚单位（CT B）作为分子内佐剂，提高VP 8 -1的免疫原性。将N-末端和C-末端融合蛋白纯化至同质，在该阶段它们形成五聚体，并且在小鼠模型中显示出比VP 8 -1/氢氧化铝混合物显著更高的免疫原性和保护功效。与VP 8 -1-CTB相比，CTB-VP 8 -1对GM 1和对VP 8特异的构象敏感的中和性单克隆抗体都显示出更高的结合活性。更重要的是，CTB-VP 8 -1比VP 8 -1-CTB引发更高滴度的中和抗体，并赋予更高的保护效力。因此，具有增强的免疫原性和免疫保护性的蛋白CTB-VP 8 -1可以被认为是进一步开发针对轮状病毒疾病的替代的、复制缺陷的、肠胃外施用的疫苗的可行候选物。
In attempts to develop recombinant subunit vaccines against rotavirus disease, it was previously shown that the N-terminal truncated VP8* protein, VP8-1 (aa26-231), is a good vaccine candidate when used for immunization in combination with Freund's adjuvant. However, this protein stimulated only weak immune response when aluminum hydroxide was used as an adjuvant. In this study, the nontoxic B subunit of cholera toxin (CTB) was employed as intra-molecular adjuvant to improve the immunogenicity of VP8-1. Both, the N-terminal and C-terminal fusion proteins, were purified to homogeneity, at which stage they formed pentamers, and showed significantly higher immunogenicity and protective efficacy than a VP8-1/aluminum hydroxide mixture in a mouse model. Compared to VP8-1-CTB, CTB-VP8-1 showed higher binding activity to both, GM1 and the conformation sensitive neutralizing monoclonal antibodies specific to VP8. More importantly, CTB-VP8-1 elicited higher titers of neutralizing antibodies and conferred higher protective efficacy than VP8-1-CTB. Therefore, the protein CTB-VP8-1, with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development of an alternative, replication-incompetent, parenterally administered vaccine against rotavirus disease.