候选无细胞百白破-Sabin株灭活脊髓灰质炎联合疫苗在大鼠上的免疫保护效果研究  

Immunoprotective effect of a candidate diphtheria, tetanus, acellular pertussis and Sabin strain inactivated poliovirus combined vaccine in rat model

作　　者：姬秋彦[1] 江文文 梁疆莉[1] 顾琴[1] 高娜[1] 马艳[1] 牟大超 史荔[1] 孙明波[1] JI Qiu-yan;JIANG Wen-wen;LIANG Jiang-li;GU Qin;GAO Na;MA Yan;MOU Da-chao;SHI Li;SUN Ming-bo(Yunnan Key Laboratory of Vaccine Research&Development on Severe Infections Diseases,Institute of Medical Biology,Chinese Academy of Medical Science&Peking Union Medical College,Kunming 650118,China)

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所云南省重大传染病疫苗研发重点实验室

出　　处：《中国医药生物技术》2020年第1期18-24,共7页Chinese Medicinal Biotechnology

基　　金：国家科技重大专项（2015ZX09101031）;中国医学科学院医学与健康科技创新工程重大协同创新项目（2016-I2M-1-019）

摘　　要：目的观察候选无细胞百白破-Sabin株灭活脊髓灰质炎联合疫苗(DTaP-sIPV)在大鼠中的免疫保护效果,为疫苗临床前研究提供依据。方法将候选疫苗DTaP-sIPV、无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗(DTaP-IPV/Hib)、吸附无细胞百白破-b型流感嗜血杆菌联合疫苗(DTaP/Hib)、百日咳疫苗效力参考品(全细胞疫苗,wP)按0、30、60 d 3剂免疫程序免疫Wistar大鼠,检测各组大鼠每剂免疫后的血清中各组分抗体水平。在免疫完成后3周,用百日咳18323株通过气雾攻击的方式感染大鼠。在感染后的第3、7、14、21和28天检测各组白细胞数、肺部菌落克隆形成数以及百日咳疫苗组分抗体变化水平。结果候选疫苗组3剂次免疫完成后PT抗体几何平均滴度(GMT,log2)为16.74,FHA抗体GMT为18.44,PRN抗体GMT为10.75,DT抗体GMT为17.34,TT抗体GMT为17.84,针对3种Sabin脊髓灰质炎病毒株(Ⅰ、Ⅱ和Ⅲ型)的抗体的GMT分别为7.57、8.41和9.70,均达到100%阳转。候选疫苗抗原组分抗体除了PRN和I型IPV外,其他组分抗体水平均与疫苗对照组相比无显著性差异。在基础免疫完成后3周对大鼠进行百日咳杆菌气雾攻击,各疫苗组均表现较好的保护效果,白细胞水平都呈现平稳状态,虽然在肺部也检测到少量细菌定植,但各疫苗组间差异不明显,且在感染后第28天都清除至检测限;而空白对照组在肺部则检测到了大量细菌定植,且在感染后第28天都并未清除至检测限,百日咳特异性的FHA和PRN抗体在感染后的第14天也出现了相应的升高。结论候选疫苗在Wistar大鼠模型上具有较好的免疫保护效果。Objective We aim to observe the immunoprotective effect of a candidate diphtheria,tetanus,acellular pertussis and Sabin strain inactivated poliovirus combined vaccine(DTaP-sIPV)in rat model for further preclinical research.Methods Candidate diphtheria,tetanus,acellular pertussis and Sabin strain inactivated poliovirus combined vaccine(DTaP-sIPV),diphtheria,tetanus,acellular pertussis,inactivated poliovirus and Haemophilus type b combined vaccine(DTaP-IPV/Hib),diphtheria,tetanus,acellular pertussis and Haemophilus type b combined vaccine(DTaP/Hib),and national potency standard for pertussis vaccine(whole pertussis vaccine,wP)were immunized with Wistar rats(8/group)according to the 0,30,and 60-day immunization schedules.The serum antibody levels of each component in each group were measured.Three weeks post immunization,the rats were infected with pertussis 18323 via aerosol injection using aerosol apparatus.The numbers of white blood cells,bacterial counting of lung,colony-forming units(CFU)from the lung tissue and specific antibodies were detected at 3,7,14,21 and 28 days after infection.Results In the candidate vaccine group,the geometric mean titer(GMT,log2)of anti-PT,anti-FHA,anti-PRN anti-DT,and anti-TT was 16.74,18.44,10.75,17.34,and 17.84,respectively.The GMT of the antibodies against the Sabin poliovirus strains(types Ⅰ,Ⅱ and Ⅲ)were 7.57,8.41 and 9.70,respectively,both achieving 100%positive conversion.In addition to PRN and type I-IPV,the antibody levels of the candidate vaccine antigen components were not significantly different from those of the vaccine control group.The rats were challenged with B.pertussis three weeks after the completion of basic immunization.Each vaccine group showed better protection,and white blood cell levels were stable.Although a small amount of bacterial colonies were detected in the lung tissues,there no obvious difference in the vaccine groups,and the bacterial colonies were cleared to the detection limit on the 28th day after infection.However,a large number of bacter

关 键 词：无细胞百白破-Sabin株脊髓灰质炎联合疫苗 免疫 感染 保护效果 

分 类 号：R392-33[医药卫生—免疫学]