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新型发热伴血小板减少综合征病毒灭活疫苗的制备及免疫原性研究

Preparation and preliminary study of inactivated vaccine for fever with thrombocytopenia syndrome virus
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摘要 目的评估和比较采用H_(2)O_(2)与β-丙内酯为灭活剂制备新型发热伴血小板减少综合征病毒(SFTSV)灭活疫苗的免疫原性。方法将SFTSV分别用H_(2)O_(2)与β-丙内酯灭活,并与铝胶佐剂配伍制成灭活疫苗免疫小鼠,持续21 d测小鼠体重、进食量、精神状态等,评估疫苗的安全性。酶联免疫吸附试验(ELISA)检测小鼠血清中SFTSV特异性抗体水平,中和实验测定小鼠血清中SFTSV中和抗体水平,使用流式细胞术测定脾脏中B细胞的募集与活化水平。结果研究制备的两种灭活疫苗均表现出良好的安全性,SFTSV中和抗体均值在免疫后8周效价均能达到1∶300以上,诱导的免疫反应均倾向于Th2型,且具有较高的B细胞的活化水平,其中H_(2)O_(2)灭活剂组诱导产生的中和抗体效价高于β-丙内酯灭活剂组。结论成功制备了两种在小鼠中诱导强烈体液免疫反应的SFTSV灭活候选疫苗,并提供了相关的免疫参数。H_(2)O_(2)作为灭活剂已显示出一定的优势,有助于开发有效的疫苗,为制备发热和血小板减少综合征病毒新型灭活疫苗提供研究依据。 Objective To evaluate and compare the immunogenicity of a novel inactivated vaccine against febrile thrombocytopenia syndrome virus(SFTSV)using H_(2)O_(2) andβ-propanelactone as inactivators.Methods SFTSV was inactivated with H_(2)O_(2) andβ-propionolactone,and the inactivated vaccine was prepared with aluminum adjuvant,and the body weight,food intake,and mental status of the mice were measured for 21 days to evaluate the safety of the vaccine.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of SFTSV-specific antibodies in the serum of mice,neutralization assay was used to determine the level of SFTSV neutralizing antibody in the serum of mice,and the recruitment and activation of B cells in the spleen were determined by flow cytometry.Results The two inactivated vaccines prepared in this study showed good safety,the average titer of SFTSV neutralizing antibody could reach more than 1∶300 at 8 weeks after immunization,the induced immune response tended to be Th2 type,and had a high activation level of B cells,up to 19.1%,and the neutralizing antibody titer induced by the H_(2)O_(2) inactivator group was higher than that of theβ-propanelactone inactivator group.Conclusion In this study,two inactivated SFTSV vaccine candidates that induced a strong humoral immune response in mice were successfully prepared,and relevant immune parameters were provided.H_(2)O_(2) has shown certain advantages as an inactivator,which is helpful for the development of effective vaccines,provides strong protection against SFTSV infection,and provides a research basis for the preparation of new inactivated vaccines for febrile and thrombocytopenia syndrome virus.
作者 杨盼 刘乐乐 田莉 韩越 赵忠欣 孙培录 郑学星 夏咸柱 郑文文 YANG Pan;LIU Lele;TIAN Li;HAN Yue;ZHAO Zhongxin;SUN Peilu;ZHENG Xuexing;XIA Xianzhu;ZHENG Wenwen(School of Public Health,Cheeloo Collage Medicine,Shandong University,Jinan 250012,China;Linyi People's Hospital of Shandong Province;Institute of Materia Medica,Shandong First Medical University&Shandong Academy of Medical Sciences;Institute of Military Veterinary Medicine,Academy of Military Medical Sciences,Academy of Military Sciences)
出处 《中国病原生物学杂志》 CSCD 北大核心 2024年第5期507-513,共7页 Journal of Pathogen Biology
基金 国家重点研发计划项目(No.2022YFC2305005) 国家自然科学基金项目(No.32170154,82102391,82272335,92269116) 山东省自然基金(No.ZR2021MC010)。
关键词 发热伴血小板减少综合征病毒 灭活疫苗 中和抗体 灭活剂 H_(2)O_(2) fever with thrombocytopenia syndrome virus inactivated vaccines neutralizing antibodies Inactivator H_(2)O_(2)
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