人呼吸道合胞病毒F-Fc蛋白不同免疫方案对小鼠免疫效果的比较  

Comparison of Immune Effects of Different Immunization Schemes Against Human Respiratory Syncytial Virus F-Fc Protein in Mice

作　　者：任虎 李海 曹蕾[1] 张燕[1] 胡宏俏 黄星湖 李海鑫 张丽 许文波[1] 刘宏图[1] REN Hu;LI Hai;CAO Lei;ZHANG Yan;HU Hongqiao;HUANG Xinghu;LI Haixin;ZHANG Li;XU Wenbo;LIU Hongtu(National Institute for Viral Diseases Control and Prevention,China CDC,NHC Key Laboratory of Medical Virology and Viral Diseases,Beijing 102206,China;Medical School,Anhui University of Science and Technology,Huainan 232001,China;Shandong First Medical University,Taian271000,China)

机构地区：[1]国家卫生健康委员会医学病毒和病毒病重点实验室,中国疾病预防控制中心病毒病预防控制所,北京102206 [2]安徽理工大学医学院,淮南232001 [3]山东第一医科大学,泰安271000

出　　处：《病毒学报》2023年第3期681-690,共10页Chinese Journal of Virology

摘　　要：人呼吸道合胞病毒(Human respiratory syncytial virus,hRSV)是全球婴幼儿和老年人严重呼吸道疾病的主要原因。hRSV感染主要局限于呼吸道,当鼻黏膜中特异性IgA抗体滴度较低时容易引起hRSV反复感染,理想的hRSV疫苗应诱导全身免疫应答,尤其是黏膜免疫。本研究应用CHO细胞表达融合蛋白F-Fc(含有hRSV F蛋白和人IgG1抗体的Fc片段),F-Fc蛋白结合CpG佐剂两次免疫小鼠,比较滴鼻免疫(Intranasal,in)和肌肉注射(Intramuscular,im)免疫安全性和有效性的差异。与佐剂对照组(CpG)相比,四种免疫方式(CpG+F-Fc/in+im,CpG+F-Fc/im+in,CpG+F-Fc/im+im和CpG+F-Fc/in+in)均能诱导高滴度中和抗体,高水平及Th1偏向的细胞免疫应答,减少肺脏病毒的滴度,但是两次滴鼻免疫组小鼠效果是最好的。同时,两次滴鼻免疫组小鼠诱导的IgA抗体最多,小鼠体重恢复速度最快,并且可以显著降低肺脏病理损伤。综上所述,在以上四种免疫方案中,两次滴鼻免疫诱导产生的免疫效果最优。Human respiratory syncytial virus(hRSV)is the leading cause of severe respiratory diseases in infants and the elderly worldwide.hRSV infection is mainly limited to respiratory tract.When the titer of specific IgA antibody on nasal mucosa is low,repeated hRSV infection will occor.The ideal hRSV vaccine should induce systemic immune response,especially mucosal immunity.In this study,CHO cells were used to express fusion protein F-Fc(containing hRSV F protein and Fc fragment of human IgG1 antibody),and F-Fc protein combined with CpG adjuvant was used to immunize mice twice.The safety and efficacy of intranasal immunization(in)and intramuscular immunization(im)were compared.Compared with adjuvant control group(CpG),four immunization groups(CpG+F-Fc/in+im,CpG+F-Fc/im+in,CpG+F-Fc/im+im and CpG+F-Fc/in+in)induced high titer neutralizing antibody,high level and Thl biased cellular immune response,and reduced the titer of lung virus.Mice immunized with two intranasal immunization showed the best effect.At the same time,the mice in the twice nasal immunization group showed the highest IgA antibodies,the fastest weight recovery rate,and significantly reduced the pathological damage in the lungs.In summary,among the above four immunization schemes,the immune effect induced by twice intranasal immunization is the best.

关 键 词：人呼吸道合胞病毒 免疫途径 安全性 有效性 

分 类 号：R392.9[医药卫生—免疫学] R373.1[医药卫生—基础医学]