中文摘要:研究分析了霍乱毒素(CTB)B亚单位作为分子内佐剂对提高VP8-1免疫原性的效果分析。试验对融合蛋白的N末端和C末端进行了纯化,构建了五聚体。应用小鼠模型分析表明,与VP8-1/氢氧化铝混合物相比,该五聚体能显著提高疫苗的免疫原性和免疫保护作用。与VP8-1-CTB相比,CTB-VP8-1表现出更高的结合活性。CTB-VP8-1产生的中和抗体滴度更高,并表现出更高的免疫保护活性。因此,蛋白CTB-VP8-1能够增强疫苗的免疫活性和免疫保护性,可用于研制抗轮状病毒的疫苗。
外文摘要: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.
外文关键词:cholera toxin B subunit; diarrhea; neutralizing antibody; rotavirus vaccine; VP8-1 protein
作者: Xue, MG; Yu, LQ; Jia, LZ; Li, YJ; Zeng, YJ; Li, TD; Ge, SX; Xia, NS
作者单位:厦门大学
期刊名称:HUMAN VACCINES & IMMUNOTHERAPEUTICS
期刊影响因子:2.146
出版年份:2016
出版刊次:11
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