吸附无细胞百日咳-白喉-破伤风-乙型肝炎-Sabin株灭活脊髓灰质炎联合疫苗加强免疫效果及安全性评价  

Booster immune effect and safety of diphtheria,tetanus,accellular pertussis,hepatitis B and inactivated poliovirus (Sabin strain) combined vaccine

作　　者：李洪哲[1] 郑惠文[1] 陈梦娇[1] 邓燕[1] 许秀雯[1] 叶慧[1] 刘小畅[1] 孙明波[1] 杨净思[1] LI Hong-zhe;ZHENG Hui-wen;CHEN Meng-jiao;DENG Yan;XU Xiu-wen;YE Hui;LIU Xiao-chang;SUN Ming-bo;YANG Jing-si(Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650118,Yunnan Province,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

出　　处：《中国生物制品学杂志》2020年第1期6-12,18,共8页Chinese Journal of Biologicals

基　　金：国家十二五“重大新药创制”科技重大专项（2015ZX09101-031）;云南省联合支持国家专项（2016GA004）

摘　　要：目的评价不同剂量配比及制备工艺的吸附无细胞百日咳-白喉-破伤风-乙型肝炎-Sabin株灭活脊髓灰质炎联合疫苗(DTaP-HepB-sIPV)免疫大鼠后加强免疫效果及安全性。方法以中、低剂量与铝佐剂相互配伍的不同sIPV配方设计4个DTaP-HepB-sIPV联合疫苗实验组,即中剂量含铝佐剂sIPV组(A组)、中剂量不含铝佐剂sIPV组(B组)、低剂量含铝佐剂sIPV组(C组)、低剂量不含铝佐剂sIPV组(D组),并设相应各组分的对照组和Infanrix hexaTM疫苗参考组。以已完成3剂基础免疫的Wistar大鼠为实验动物,在全程免疫第16个月接种1剂次加强免疫,进行安全性评价,并比较加强免疫前后各组大鼠血清中各组分抗体水平、中和抗体几何平均滴度(GMT)及阳转率,同时观察加强免疫对大鼠外周血中淋巴细胞的影响。结果加强免疫后未观察到不良反应,大鼠接种部位未见红肿、硬结、溃烂等现象,且各组大鼠体重维持稳定。加强免疫后30 d,各组大鼠各型别脊灰病毒中和抗体均为阳性,Ⅰ、Ⅱ、Ⅲ型抗体阳转率A组分别为100%、71.4%、85.7%,B组分别为71.4%、85.7%、100%,C组分别为80%、80%、100%,D组分别为71.4%、100%、85.7%;A组诱导的各型别脊灰病毒中和抗体GMT均高于B组,且可达到或超过参考组;B、D组诱导产生的各型脊灰病毒中和抗体GMT均能达到同等剂量相应对照组水平。加强免疫后,各组百白破各组分抗体GMT有5~106倍增长,联合疫苗实验组GMT与对照组相比,总体上差异无统计学意义(P>0.05)。加强免疫后,乙肝抗体阳转率乙肝对照组为66.7%,B组为55.6%,C组为50%,A组为16.7%,D组为14.3%,参考组为0%;各组Anti-HBsAg水平有不同程度的升高,但两两相比,各组差异均无统计学意义(P>0.05)。结论DTaPHepB-sIPV具有良好的安全性,sIPV中剂量含铝佐剂的DTaP-HepB-sIPV联合疫苗所诱导的各抗体水平更加稳定持久,可作为未来疫苗最佳配比的参考。Objective To evaluate the booster immune effect and safety of diphtheria,tetanus,acellular pertussis,hepatitis B and inactivated poliovirus(Sabin strain)combined vaccine(DTaP-HepB-sIPV)prepared at various ratios of dosages by various procedures in rats.Methods Four experimental groups of DTaP-HepB-sIPV vaccine were designed in this study based on aluminum adjuvant and the dosage of sIPV.The sIPV in group A was at a moderate dosage and contained aluminum adjuvant,while that in group B was at a moderate dosage and contained no aluminum adjuvant,that in group C was at a low dosage and contained aluminum adjuvant,and that in group D was at a low dosage and contained no aluminum adjuvant,using the corresponding components or the Infanrix hexaTM vaccine as control.Wistar rats which had completed three doses of primary immunization were used as animal models and inoculated with a booster dose at month 16 after primary immunization to evaluate the safety.The antibody levels as well as GMTs and positive conversion rates of neutralizing antibody of rats in various groups before and after booster immunization were compared.Meanwhile,the effect of booster immunization on lymphocytes in peripheral blood of rats was observed.Results After booster immunization,no adverse reactions were observed in various groups,while no redness,swelling,induration,festering and other phenomena were found in the inoculated site,and the body weight of rats in various groups remained stable.All the poliovirus neutralizing antibodies of various types were positive in various groups 30 d after booster immunization,while the seroconversion rates of typesⅠ,ⅡandⅢneutralizing antibodies against poliovirus were 100%,71.4%and 85.7%in group A,71.4%,85.7%and 100%in group B,80%,80%and 100%in group C,and 71.4%,100%and 85.7%in group D,respectively.The GMTs of neutralizing antibody against poliovirus of various types induced in group A were higher than those in group B,which reached or exceeded those in Infanrix hexaTM control group.However,the GMTs indu

关 键 词：吸附无细胞百日咳 白喉 破伤风 乙型肝炎 Sabin株灭活脊髓灰质炎 加强免疫 安全性 

分 类 号：R378.42[医药卫生—病原生物学] R392-33[医药卫生—基础医学]