DTacP-sIPV或DTacP-IPV/Hib基础免疫大鼠后加强免疫百白破联合疫苗Tdap的体液免疫评价

Effects of booster vaccination with tetanus toxoid,reduced diphtheria and acellular pertussis combined vaccine(Tdap)after vaccination of rats with DTacP-sIPV or DTacP-IPV/Hib

目的观察组分无细胞百白破-Sabin株脊髓灰质炎联合疫苗(DTacP-sIPV)或无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗(DTacP-IPV/Hib)基础免疫大鼠后加强免疫破伤风类毒素、降低抗原含量的白喉毒素和无细胞百日咳联合疫苗(Tdap)是否产生免疫加强效果,为候选青少年及成人Tdap疫苗提供临床前研究参考。方法将自主研发的DTacP-sIPV和已上市的DTacP-IPV/Hib按0、1、2月3剂免疫程序分别免疫Wistar大鼠,检测免疫前和每剂次免疫后各组大鼠血清中各组分抗体水平。基础免疫完成10个月后,用候选Tdap加强免疫1次,并检测加强免疫前和免疫1个月、6个月后血清中各组分抗体水平。结果3剂次基础免疫1个月后,DTacP-sIPV组抗白喉类毒素(diphtheria toxoid,DT)、抗破伤风类毒素(tetanus toxoid,TT)、抗百日咳毒素(pertussis toxin,PT)、抗丝状血凝素(filamentous hemagglutinin,FHA)和抗百日咳黏附素(pertactin,PRN)抗体的几何平均滴度(GMT,Log2)分别为17.41、18.34、18.11、19.93、13.91,血清阳转率均达到100%;基础免疫10个月后,抗DT、抗TT、抗PT、抗FHA和抗PRN抗体的GMT分别下降至15.17、14.26、13.60、14.51、10.39,血清阳转率维持在89%以上。Tdap加强免疫1个月后,DTacP-sIPV组和DTacP-IPV/Hib组抗DT、抗TT、抗PT、抗FHA抗体的GMT分别为16.49和17.26、16.80和17.63、16.70和17.74、18.48和19.26,血清阳转率均达到100%,组间差异无统计学意义(P均>0.05);抗PRN抗体的GMT分别为13.07和11.00,血清阳转率为100%和88%,DTacP-sIPV组高于DTacP-IPV/Hib组(P<0.05)。Tdap加强免疫6个月后,DTacP-sIPV组和DTacP-IPV/Hib组抗DT、抗TT、抗PT、抗FHA和抗PRN抗体的GMT分别下降至15.74和14.87、15.07和15.14、14.84和15.73、16.62和16.37、11.44和9.96,血清阳转率维持在88%以上。结论候选疫苗Tdap在基础免疫接种DTacP-sIPV和DTacP-IPV/Hib的Wistar大鼠模型加强免疫中可诱导产生良好的体液免疫应答,但抗体滴度随时间推移而衰减。

Objective To evaluate the effects of a booster immunization with a candidate tetanus toxoid,reduced diphtheria toxoid and acellular pertussis combined vaccine(Tdap)in a rat model after primary vaccination with diphtheria,tetanus,acellular pertussis and Sabin strain inactivated poliovirus combined vaccine(DTacP-sIPV)or diphtheria,tetanus,acellular pertussis,inactivated poliovirus and haemophilus type b combined vaccine(DTacP-IPV/Hib)for further preclinical study.Methods Wistar rats were randomly divided into three groups and respectively immunized with a self-developed DTacP-sIPV,a marketed DTacP-IPV/Hib and normal saline at 0,1,and 2 months of age.Serum levels of antibody against each component in each group were detected before immunization and after each dose.A booster dose of the candidate Tdap was given 10 months after primary immunization.Serum levels of antibody against each component in each group were detected before,1 month and 6 months after the booster immunization.Results One month after three doses of primary immunization,the geometric mean titers(GMT,Log2)of antibodies against diphtheria toxoid(DT),tetanus toxoid(TT),pertussis toxin(PT),filamentous hemagglutinin(FHA)and pertactin(PRN)in the DTacP-sIPV group were 17.41,18.34,18.11,19.93 and 13.91,respectively,and the seroconversion rates of these components all reached 100%.Ten months after primary immunization,the GMTs of antibodies against DT,TT,PT,FHA and PRN decreased to 15.17,14.26,13.60,14.51 and 10.39,respectively,and the seroconversion rates remained above 89%.One month after booster immunization,the GMTs of antibodies against DT,TT,PT and FHA in the DTacP-sIPV and DTacP-IPV/Hib groups were 16.49/17.26,16.80/17.63,16.70/17.74 and 18.48/19.26,respectively,and the seroconversion rates of these components all reached 100%with no significant difference between the two groups(P>0.05).The GMTs of anti-PRN antibody in the DTacP-sIPV and DTacP-IPV/Hib groups were 13.07 and 11.00,and the seroconversion rates were 100%and 88%,which were higher in the DTacP-sIPV group than in the DTacP-IPV/Hib group(P<0.05).Six months after booster immunization,the GMTs of antibodies against DT,TT,PT,FHA and PRN in the DTacP-sIPV and DTacP-IPV/Hib groups decreased to 15.74/14.87,15.07/15.14,14.84/15.73,16.62/16.37 and 11.44/9.96,respectively,and the seroconversion rates remained above 88%.Conclusions Booster vaccination with the candidate Tdap vaccine induces humoral immune response following primary immunization with DTacP-sIPV or DTacP-IPV/Hib in the Wistar rat model,while the antibody titer decreases with time.