首页|期刊导航|河南农业大学学报|猪链球菌多表位融合疫苗MVPLM-SS的构建及免疫效果评价

猪链球菌多表位融合疫苗MVPLM-SS的构建及免疫效果评价OA

Construction and immunogenicity evaluation of a multi-epitope fusion vaccine MVPLM-SS against Streptococcus suis

中文摘要英文摘要

[目的]以PdhA、Ldh和MalX的优势抗原表位为基础构建多表位候选疫苗,以期开发具有广谱保护作用的猪链球菌(Streptococcus suis,SS)新型疫苗.[方法]运用免疫信息学方法预测猪链球菌免疫原性蛋白(PdhA、Ldh、MalX)的B细胞表位、细胞毒性T淋巴细胞表位和辅助性T淋巴细胞表位,将评分较高且位于蛋白结构表面的优势抗原表位通过连接子AAY、KK和GPGPG连接,构建猪链球菌重组多表位融合疫苗(multi-epitope vaccine PdhA-Ldh-MalX-SS,MVPLM-SS).通过临床观察、抗体滴度检测、细胞因子测定和生存曲线分析等方法评估疫苗安全性和免疫原性.[结果]共筛选出14条优势表位肽段,并基于此构建多表位融合蛋白MVPLM-SS.该蛋白具有良好亲水性、热稳定性与结构稳定性,分子对接显示其能与Toll样受体TLR4有效结合.成功构建重组表达质粒 pET28a(+)-sumo-MVPLM-SS,并诱导表达出约 63 kD的目的蛋白.与磷酸盐缓冲液/佐剂对照组相比,MVPLM-SS免疫小鼠可显著提升血清中IgG抗体水平,以及IL-4及IFN-γ质量浓度,有效延长小鼠的存活时间,并减轻脑和肺脏组织病理损伤.[结论]构建的多表位融合疫苗MVPLM-SS结构合理,能在大肠杆菌中高效表达,可诱导小鼠产生特异性体液免疫应答,有效减轻猪链球菌感染导致的组织病理损伤,是开发高效、广谱猪链球菌疫苗的有效策略.

[Objective]Based on the immunodominant epitopes of PdhA,Ldh,and MalX,a multi-epitope candidate vaccine against Streptococcus suis(SS)was designed with the aim of developing a novel vaccine with broad-spectrum protection.[Method]Using immunoinformatics methods,the BCL epitopes,CTL epitopes,and HTL epitopes were predicted from the immunogenic proteins PdhA,Ldh,and MalX of Streptococcus suis.High-scoring surface-exposed immunodominant epitopes were then linked via AAY,KK,and GPGPG linkers to construct the multi-epitope vaccine MVPLM-SS(multi-epitope vaccine PdhA-Ldh-MalX-SS).Finally,its safety and immunogenicity were evaluated through clinical monitoring,antibody titer detection,cytokine assays,and survival curve analysis.[Result]A total of 14 dominant epitope peptides were screened and used to construct the multi-epitope fusion protein MVPLM-SS.The resulting protein exhibited favorable hydrophilicity,thermal stability,and structural stability.Molecular docking analysis further predicted effective binding between MVPLM-SS and Toll-like receptor 4(TLR4).Subsequently,the recombinant expression plasmid pET28a(+)-sumo-MVPLM-SS was successfully constructed,and the target protein of approximately 63 kD was expressed.Compared with the PBS/adjuvant control group,MVPLM-SS immunization significantly raised serum IgG level,IL-4,and IFN-γ mass concentrations,prolonged survival,and mitigated histopathological damage in the brain and lung of mice.[Conclusion]The designed multi-epitope fusion vaccine MVPLM-SS exhibited a rational structure and was efficiently expressed in Escherichia coli.In mice,it induced robust humoral immune responses and significantly attenuated histopathological lesions caused by Strepto-coccus suis infection.These findings support MVPLM-SS as a promising candidate for the development of broad-spectrum vaccines against this pathogen.

叶思茹;胡金旺;郭子涵;李宇航;祖少坡;夏璐;张越

河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046||河南省动物性食品病原体监控重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046||河南省动物性食品病原体监控重点实验室,河南 郑州 450046河南农业大学动物医学院/动物病原与生物安全教育部重点实验室,河南 郑州 450046||河南省动物性食品病原体监控重点实验室,河南 郑州 450046

农业科技

猪链球菌抗原表位融合蛋白多表位融合疫苗免疫保护

Streptococcus suisantigenic epitopefusion proteinmulti-epitope fusion vaccineimmune protection

《河南农业大学学报》 2026 (5)

833-844,12

国家自然科学基金项目(32102673)中国博士后科学基金面上项目(2020M682297)

10.16445/j.cnki.1000-2340.20260710.001

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