壳寡糖对猪蓝耳病灭活疫苗的免疫佐剂活性及作用机制研究  

Enhanced immunogenicity of porcine reproductive and respiratory syndrome vaccine by chitosan oligosaccharides

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作  者:孙照淋 魏玉华 王倬 杜昱光[4] 段秀英 贾培媛[4] 张贵强 SUN Zhaolin;WEI Yuhua;WANG Zhuo;DU Yuguang;DUAN Xiuying;JIA Peiyuan;ZHANG Guiqiang(College of Life Sciences,Qingdao Agricultural University,Qingdao 266109,China;Medical Science and Technology Innovation Center,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250117,China;Vascular Surgery,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China;Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China)

机构地区:[1]青岛农业大学生命科学学院,山东青岛266109 [2]山东第一医科大学<山东省医学科学院>医学科技创新中心,山东济南250117 [3]山东第一医科大学附属省立医院血管外科,山东济南250021 [4]中国科学院过程工程研究所,北京100190

出  处:《药学研究》2025年第3期217-223,256,共8页Journal of Pharmaceutical Research

基  金:国家重点研发计划项目(No.2023YFC2308000);山东省立医院科研孵育基金项目(No.2022FY087);山东省中医药科技计划青年项目(No.Q-2023127)。

摘  要:目的探讨新型佐剂壳寡糖(COS)对猪蓝耳病灭活疫苗(PRRSV)的佐剂效应。方法本研究分别将不同聚合度、不同脱乙酰度的COS与PRRSV联合应用免疫BALB/c小鼠,ELISA法分别测定免疫后小鼠血清的总IgG抗体及其亚型的滴度,筛选具有佐剂活性的COS,进而在细胞和动物水平进行COS佐剂免疫活性机理分析。结果与单独免疫PRRSV相比,不同结构的COS联合免疫显著提高了小鼠血清中总IgG抗体及其各亚型的水平,并且可以促进免疫小鼠脾脏淋巴细胞增殖和巨噬细胞的吞噬作用,增加抗原特异性CD4^(+)和CD8^(+)细胞数,调节细胞因子分泌。其分子机制可能与促进巨噬细胞Toll样受体表达进而增加其对PRRSV的抗原呈递相关。结论COS是一种安全有效的新型PRRSV疫苗佐剂。Objective To investigate the adjuvant effect of chitosan oligosaccharides(COS)on the inactivated porcine reproductive and respiratory syndrome vaccine(PRRSV).Methods BALB/c mice were immunized with PRRSV alone or in combination with COSs that possess varying degrees of acetylation(DA)and degrees of polymerization(DP).The adjuvant effect was evaluated by determining the serum total IgG levels and the titers of its various subtypes against PRRSV using ELISA.Additionally,the immunological mechanisms were explored both in vitro and in vivo.Results Compared to the PRRSV alone,COSs significantly increased the antibody levels of total IgG and its subtypes,promoted lymphocyte proliferation,increased the numbers of antigen-specific CD4^(+)and CD8^(+)T cells in the spleens,and initiated a two-way regulation of cytokine secretion.The molecular mechanism may be associated with the overexpression of Toll-like receptors(TLRs)on macrophages,which subsequently promotes PRRSV presentation.Conclusion COSs may serve as safe and effective candidates for the development of new adjuvants for PRRSV.

关 键 词:壳寡糖 猪蓝耳病灭活疫苗 免疫佐剂 乙酰化程度 聚合度 

分 类 号:R967[医药卫生—药理学]

 

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